RESUMEN
AIM: To investigate whether electroacupuncture (EA) at ST25 affects jejunal motility in vivo and if so, whether a sympathetic pathway is involved. METHODS: Jejunal motility was assessed using a manometric balloon placed in the jejunum approximately about 3-5 cm away from the suspensory ligament of the duodenum in anesthetized animals. The effects of EA at ST25 were measured in male Sprague-Dawley rats, some of which were treated with propranolol or clenbuterol (EA intensities: 1, 3, 5, 7, and 9 mA), and in male transient receptor potential vanilloid-1 (TRPV1) (capsaicin receptor) knockout mice (EA intensities: 1, 2, and 4 mA). RESULTS: Anesthetized rats exhibited three types of fasting jejunal motor patterns (types A, B, and C), and only type C rats responded to EA stimulation. In type C rats, EA at ST25 significantly suppressed the motor activity of the jejunum in an intensity-dependent manner. The inhibitory effect of EA was weakened by propranolol (ß adrenoceptor antagonist) and disappeared with clenbuterol (ß adrenoceptor agonist) induced inhibition of motility, suggesting that the effect of EA on motility is mediated via a sympathetic pathway. Compared with wild-type mice, EA at ST25 was less effective in TRPV1 knockout mice, suggesting that this multi-modal sensor channel participates in the mechanism. CONCLUSION: EA at ST25 was found to inhibit jejunal motility in an intensity-dependent manner, via a mechanism in which sympathetic nerves and TRPV1 receptors play an important role.
Asunto(s)
Puntos de Acupuntura , Electroacupuntura/métodos , Motilidad Gastrointestinal , Yeyuno/inervación , Sistema Nervioso Simpático/metabolismo , Canales Catiónicos TRPV/metabolismo , Agonistas Adrenérgicos beta/farmacología , Antagonistas Adrenérgicos beta/farmacología , Animales , Clenbuterol/farmacología , Motilidad Gastrointestinal/efectos de los fármacos , Genotipo , Masculino , Ratones Noqueados , Actividad Motora , Fenotipo , Propranolol/farmacología , Ratas Sprague-Dawley , Reflejo , Sistema Nervioso Simpático/efectos de los fármacos , Canales Catiónicos TRPV/deficiencia , Canales Catiónicos TRPV/genética , Factores de TiempoRESUMEN
beta2-Adrenergic agonists (BAAs) act as repartitioning agents in domestic animals by redistributing nutrients away from adipose tissue and towards muscle accretion. The mechanism involves altering the rates of protein degradation and synthesis. The aim of this study was to test the effects of chronic feeding of the BAAs clenbuterol (CLEN) and ractopamine (RACT) on rainbow trout (RBT) muscle. Specifically, we examined the activities and mRNA levels of genes in the major proteolytic pathways including calpains, the multi-catalytic proteasome and cathepsins, and the mRNA levels of genes encoding the myofibrillar proteins, fast-twitch and slow-twitch myosin heavy chains (f-MHC and s-MHC, respectively), and the cytoskeletal protein, beta-actin. RACT feeding significantly increased mRNA transcripts of the calpain catalytic subunit (Capn1), the regulatory subunit (cpns), and the calpastatin large isoform (CAST-L), without affecting the calpain enzyme activity. CLEN feeding significantly increased mRNA levels of the proteasome alpha subunit without a corresponding change in 20S enzyme activity. RACT significantly decreased cathepsin D activity without affecting mRNA levels suggesting that the action of RACT may be at the post-transcriptional level. In addition, both CLEN and RACT significantly increased mRNA transcripts of f-MHC and beta-actin genes suggesting an anabolic role of BAAs on myofibrillar and cytoskeletal proteins. Neither CLEN nor RACT altered mRNA expression of the s-MHC gene indicating no transformation of muscle fiber-types. This study supports a role for BAAs in inducing RBT muscle accretion by altering both protein synthesis and degradation.
Asunto(s)
Agonistas Adrenérgicos beta/efectos adversos , Proteínas Musculares/metabolismo , Músculos/efectos de los fármacos , Oncorhynchus mykiss/metabolismo , Péptido Hidrolasas/metabolismo , Factor de Transcripción Activador 1/metabolismo , Adenilil Ciclasas/metabolismo , Secuencia de Aminoácidos , Alimentación Animal/efectos adversos , Animales , Calpaína/metabolismo , Catepsinas/metabolismo , Clenbuterol/farmacología , AMP Cíclico/metabolismo , ADN Complementario , Datos de Secuencia Molecular , Músculos/enzimología , Fenetilaminas/farmacología , Complejo de la Endopetidasa Proteasomal/metabolismo , Receptores Adrenérgicos beta 2/metabolismo , Homología de Secuencia de AminoácidoRESUMEN
OBJECTIVE: Chronic mechanical unloading induces left ventricular (LV) atrophy, which may impair functional recovery during support with an LV-assist device. Clenbuterol, a beta2-adrenergic receptor (AR) agonist, is known to induce myocardial hypertrophy and might prevent LV atrophy during LV unloading. Furthermore, beta2-AR stimulation is reported to improve Ca2+ handling and contribute to antiapoptosis. However, there is little information on the effects of clenbuterol during LV unloading. METHODS AND RESULTS: We investigated LV atrophy and function after LV unloading produced by heterotopic heart transplantation in isogenic rats. After transplantation, rats were randomized to 1 of 2 groups (n=10 each). The clenbuterol group received 2 mg.kg(-1).d(-1) of the drug for 2 weeks; the control group received normal saline. The weight of unloaded control hearts was 48% less than that of host hearts after 2 weeks of unloading. Clenbuterol significantly increased the weight of the host hearts but did not prevent unloading-induced LV atrophy. Papillary muscles were isolated and stimulated, and there was no difference in developed tension between the 2 groups. However, the inotropic response to the beta-AR agonist isoproterenol significantly improved in the clenbuterol group. The mRNA expression of myocardial sarco(endo)plasmic reticulum Ca2+-ATPase 2a (SERCA2a) and fetal gene shift (myosin heavy chain [MHC] mRNA isozyme) was also significantly improved by clenbuterol treatment. There was no difference in beta1-AR mRNA expression between the 2 groups. In contrast, beta2-AR mRNA was significantly decreased in the clenbuterol-treated, unloaded heart. This indicates that clenbuterol may downregulate beta2-ARs. In the evaluation of apoptosis, mRNA expression of caspase-3, which is the central pathway for apoptosis, tended to be better in the clenbuterol group. CONCLUSIONS: During complete LV unloading, clenbuterol did not prevent myocardial atrophy but improved gene expression (SERCA2a, beta-MHC) and beta-adrenergic responsiveness and potentially prevented myocardial apoptosis. However, chronic administration of clenbuterol may be associated with downregulation of beta2-ARs.
Asunto(s)
Agonistas Adrenérgicos beta/uso terapéutico , Clenbuterol/uso terapéutico , Corazón/efectos de los fármacos , Agonistas Adrenérgicos beta/farmacología , Animales , Atrofia , ATPasas Transportadoras de Calcio/biosíntesis , ATPasas Transportadoras de Calcio/genética , Caspasa 3 , Caspasas/biosíntesis , Caspasas/genética , Clenbuterol/farmacología , Regulación hacia Abajo/efectos de los fármacos , Evaluación Preclínica de Medicamentos , Inducción Enzimática/efectos de los fármacos , Regulación de la Expresión Génica/efectos de los fármacos , Trasplante de Corazón , Ventrículos Cardíacos/efectos de los fármacos , Ventrículos Cardíacos/patología , Ventrículos Cardíacos/fisiopatología , Isoproterenol/farmacología , Masculino , Contracción Miocárdica/efectos de los fármacos , Miocardio/patología , Cadenas Pesadas de Miosina/biosíntesis , Cadenas Pesadas de Miosina/genética , Tamaño de los Órganos , Músculos Papilares/efectos de los fármacos , Músculos Papilares/fisiopatología , Isoformas de Proteínas/biosíntesis , Isoformas de Proteínas/genética , ARN Mensajero/biosíntesis , ARN Mensajero/genética , Distribución Aleatoria , Ratas , Ratas Endogámicas Lew , Receptores Adrenérgicos beta 1/biosíntesis , Receptores Adrenérgicos beta 1/genética , Receptores Adrenérgicos beta 2/biosíntesis , Receptores Adrenérgicos beta 2/efectos de los fármacos , Receptores Adrenérgicos beta 2/genética , ATPasas Transportadoras de Calcio del Retículo Sarcoplásmico , Estrés Mecánico , Trasplante Heterotópico , Trasplante Isogénico , Función Ventricular Izquierda/efectos de los fármacosRESUMEN
Illegal dietary supplementation with beta(2)-agonists has been shown to increase protein deposition and decrease fat accretion in domestic animals. In poultry the metabolic and endocrine responses to beta(2)-agonists are not fully elucidated. In this trial the effects of dietary clenbuterol (1 p.p.m.) and cimaterol (1 p.p.m.) on muscle composition and endocrine response of male broiler chickens were studied. Dietary clenbuterol induced a slight, but in general not significant, improvement of zootechnical performances and carcass yields. Chemical composition of muscle was not influenced by dietary treatments, even if a slight improvement of protein content was observed in treated groups. No effects on fatty acid composition of meat were detected. Both clenbuterol and cimaterol treatments caused a downregulation in testicular androgen receptors and in pulmonary, cardiac and central nervous system beta-adrenergic receptors.
Asunto(s)
Agonistas Adrenérgicos beta/administración & dosificación , Composición Corporal/efectos de los fármacos , Pollos/metabolismo , Clenbuterol/administración & dosificación , Etanolaminas/administración & dosificación , Músculo Esquelético/efectos de los fármacos , Receptores Androgénicos/efectos de los fármacos , Agonistas Adrenérgicos beta/farmacología , Alimentación Animal , Animales , Pollos/anatomía & histología , Pollos/crecimiento & desarrollo , Clenbuterol/farmacología , Suplementos Dietéticos , Regulación hacia Abajo/efectos de los fármacos , Etanolaminas/farmacología , Masculino , Músculo Esquelético/metabolismo , Distribución Aleatoria , Receptores Adrenérgicos beta/efectos de los fármacos , Receptores Adrenérgicos beta/metabolismo , Receptores Androgénicos/metabolismo , Aumento de PesoRESUMEN
BACKGROUND: Muscle wasting and dysfunction is a significant problem in prolonged exposure to microgravity. HYPOTHESIS: This study tested the hypothesis that a beta-adrenergic agonist (clenbuterol) could attenuate the effects of 14 d of unweighting on mixed fiber type skeletal muscle. METHODS: Female, Sprague-Dawley rats were maintained in cages as: 1. controls (C; n = 12); 2. hindlimb suspended via tail casting (HLU; n = 12); 3. clenbuterol injected daily (3 mg x kg(-1)) (CL; n = 10); or 4. hindlimb suspended and injected with clenbuterol daily (3 mg x kg(-1)) (HLU + CL; n = 12). RESULTS: At the end of the study, both CL and HLU + CL had higher body weights compared with HLU (p < 0.05). Gastrocnemius mass (wet weight and muscle weight/body weight) and maximal tetanic force were significantly decreased during HLU (p < 0.05) (mean +/- SE; mass: C = 1.6 +/- 0.04 g, HLU = 1.2 +/- 0.05 g force: C = 3483 +/- 113 g, HLU = 2765 +/- 52 g). Clenbuterol attenuated the decrease in both mass and force generation (mass: HLU + CL = 1.4 +/- 0.04 g; force: HLU + CL = 3162 +/- 135). Twitch tension during HLU (1057 +/- 72 g) was significantly less (p < 0.05) than during C (1362 +/- 61 g), and clenbuterol did not attenuate this loss. HLU caused a decrease (p < 0.05) in force at 30 Hz and decreased one-half relaxation time (1/2 RT) (p < 0.05) from 30 +/- 2 to 25 +/- 2 ms. Clenbuterol caused further decreases (p < 0.05) in both force (20 and 30 Hz) and 1/2 RT. CONCLUSIONS: These data suggest that a beta-adrenergic agonist may be of benefit in attenuating wasting and the reduced maximal force seen during periods of unweighting in mixed fiber type muscle.
Asunto(s)
Agonistas Adrenérgicos beta/uso terapéutico , Clenbuterol/uso terapéutico , Modelos Animales de Enfermedad , Suspensión Trasera/efectos adversos , Atrofia Muscular/etiología , Atrofia Muscular/prevención & control , Agonistas Adrenérgicos beta/farmacología , Animales , Peso Corporal/efectos de los fármacos , Peso Corporal/fisiología , ATPasas Transportadoras de Calcio/efectos de los fármacos , ATPasas Transportadoras de Calcio/fisiología , Clenbuterol/farmacología , Evaluación Preclínica de Medicamentos , Femenino , Inyecciones Intramusculares , Contracción Muscular/efectos de los fármacos , Contracción Muscular/fisiología , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/fisiología , Atrofia Muscular/patología , Atrofia Muscular/fisiopatología , Tamaño de los Órganos/efectos de los fármacos , Tamaño de los Órganos/fisiología , Ratas , Ratas Sprague-Dawley , ATPasas Transportadoras de Calcio del Retículo SarcoplásmicoRESUMEN
The effects of lipoic acid (LA) on muscle growth, metabolic response and hepatic respiration in broilers treated with or without clenbuterol (CLE) were examined. In 4-week-old chickens, dietary LA administration (100 mg x kg(-1)) enhanced the beta-adrenergic response of plasma nonesterified fatty acid with an intravenous injection of CLE (50 microg x kg(-1), estimated from the response area for 120 min (-7,860 vs. 874 micromol x L(-1) min in control and LA-treated groups, respectively; P < 0.05). When chickens received long-term oral administration of CLE (0.25 mg x kg(-1)) for 30 d, LA interfered with the repartitioning action of CLE, decreased abdominal fat weight (P < 0.05) and increased protein concentration of the breast muscle (P < 0.05), in 7-week-old chickens. In addition, the LA supplementation alone increased both plasma nonesterified fatty acid (P < 0.05) and triacylglycerol (P < 0.05), whereas these effects were not associated with CLE administration. These findings suggest that the dietary LA level used stimulates rapid lipolytic response of plasma nonesterified fatty acid to CLE injection and fatty acid turnover between adipose tissue and the liver, but does not facilitate the repartitioning action of CLE during long-term treatment in broilers.
Asunto(s)
Agonistas Adrenérgicos beta/farmacología , Antioxidantes/farmacología , Pollos/metabolismo , Clenbuterol/farmacología , Metabolismo de los Lípidos , Ácido Tióctico/farmacología , Tejido Adiposo/efectos de los fármacos , Tejido Adiposo/crecimiento & desarrollo , Tejido Adiposo/metabolismo , Administración Oral , Agonistas Adrenérgicos beta/administración & dosificación , Animales , Antioxidantes/administración & dosificación , Antioxidantes/metabolismo , Glucemia/metabolismo , Peso Corporal/efectos de los fármacos , Pollos/crecimiento & desarrollo , Clenbuterol/administración & dosificación , Ácidos Grasos no Esterificados/sangre , Femenino , Inyecciones Intravenosas/veterinaria , Lipólisis , Hígado/efectos de los fármacos , Hígado/metabolismo , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/crecimiento & desarrollo , Músculo Esquelético/metabolismo , Consumo de Oxígeno/efectos de los fármacos , Ácido Tióctico/administración & dosificación , Ácido Tióctico/metabolismo , Triglicéridos/metabolismoRESUMEN
1. We examined the effects of thiamine-hydrochloride (10 mg/kg body weight) and a beta-agonist, clenbuterol (50 microg/kg body weight), on plasma metabolites and hepatic oxygen consumption in female broiler chicks. 2. Clenbuterol, thiamine or both, dissolved in saline, were injected into thigh muscle on 2, 4 and 6 d of age. At 7 d of age blood samples in each treatment group were obtained and breast muscle and liver were weighed; liver slices were used for measurement of oxygen consumption. 3. Body weight gain was reduced by clenbuterol. Thiamine increased breast muscle weight as a proportion of body weight regardless of clenbuterol dose. Clenbuterol increased relative liver weight markedly, especially when chicks received thiamine also. 4. Clenbuterol increased plasma free fatty acid concentration in chicks treated with thiamine. Thiamine decreased plasma triglyceride regardless of clenbuterol dose. Plasma glucose concentration was decreased by both thiamine and clenbuterol. 5. The absolute rate of oxygen consumption in liver slices was greater in the thiamine-treated chicks; clenbuterol did not affect hepatic oxygen consumption. 6. These findings suggest that thiamine-induced energy expenditure results not only from thermogenesis in the liver, but also from increasing energy utilisation for muscle hypertrophy and this vitamin supplementation facilitates the lipolytic effects of the beta-agonist.
Asunto(s)
Glucemia/metabolismo , Composición Corporal/efectos de los fármacos , Clenbuterol/farmacología , Ácidos Grasos no Esterificados/sangre , Hígado/metabolismo , Consumo de Oxígeno/efectos de los fármacos , Tiamina/farmacología , Triglicéridos/sangre , Agonistas Adrenérgicos beta/administración & dosificación , Agonistas Adrenérgicos beta/farmacología , Animales , Pollos , Clenbuterol/administración & dosificación , Femenino , Inyecciones Intramusculares , Hígado/efectos de los fármacos , Hígado/crecimiento & desarrollo , Desarrollo de Músculos , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/crecimiento & desarrollo , Tamaño de los Órganos/efectos de los fármacos , Tiamina/administración & dosificación , Aumento de Peso/efectos de los fármacosRESUMEN
BACKGROUND: Skeletal muscle assist (SMA) may be limited by loss of power, slowing of contraction and relaxation, and atrophy of the transformed latissimus dorsi muscle (LD). Clenbuterol (clen), a beta2-adrenergic receptor agonist, was used to improve the performance of trained skeletal muscle in sheep. METHODS AND RESULTS: The following 4 groups were used: A (n=6), untrained controls; B (n=6), left LD progressively transformed toward a slow-twitch and fatigue-resistant phenotype by electrical stimulation over 12 weeks (2.5 to 5 V, 240- microsec pulse duration, 35 Hz, 3 to 6 pulses per burst, and up to 40 bursts per minute); C (n=6), clen-treated (0.5 mg/kg SC) for 12 weeks; and D (n=6), clen+trained. In a terminal experiment, the mobilized LD was wrapped around a rubber aorta of a mock circulation and stimulated to contract 40 times per minute. Group A had an initial mean pressure augmentation (DeltaP) of 24.6 mm Hg and stroke power of 2.28 W/kg, but both fell to <20% of their original values by 15 minutes because of fatigue (P<0.005). Group B was fatigue-resistant, with a DeltaP and stroke power at 60 minutes of 13 mm Hg (70% of initial) and 0.34 W/kg (39% of initial), respectively. The performance of group C was similar to that of controls. In group D, however, the muscles were stronger at all time points than in B, with a DeltaP of 23 mm Hg and stroke power of 2.66 W/kg at 60 minutes (P<0.01). The speeds of contraction (+dP/dt:DeltaP) and relaxation (-dP/dt:DeltaP) were significantly greater in group D than B. Protein analyses showed group D to have only a trend toward greater abundance of the fast isoforms of myosin heavy chain and sarcoplasmic reticulum Ca2+-ATPase (P>0.1). CONCLUSIOINS: ++Clen improves the performance of trained skeletal muscle in a model of aortomyoplasty by unknown mechanisms. These findings may have important implications in SMA.
Asunto(s)
Agonistas Adrenérgicos beta/farmacología , Clenbuterol/farmacología , Corazón Auxiliar , Contracción Muscular/efectos de los fármacos , Músculo Esquelético/efectos de los fármacos , Animales , Peso Corporal/efectos de los fármacos , Evaluación Preclínica de Medicamentos , Estimulación Eléctrica , Femenino , Modelos Lineales , Proteínas Musculares/química , Relajación Muscular/efectos de los fármacos , Tamaño de los Órganos/efectos de los fármacos , OvinosRESUMEN
Stimulation of glucocorticoid or beta-adrenergic receptors (BAR) has been shown to increase nerve growth factor (NGF) biosynthesis in adult rat brain. Little is known about the role of these receptors in the regulation of NGF expression in neonatal and aged brain. We have examined the effect of the synthetic glucocorticoid dexamethasone (DEX) and the BAR agonist clenbuterol (CLE) on the levels of NGF mRNA in neonatal (8 day old), adult (3 month old) and aged (24 month old) rats. By 3 h, DEX (0.5 mg/kg, s.c.) evoked a comparable increase in NGF mRNA in the cerebral cortex and hippocampus in both 8-day and 3-month-old rats. In contrast, CLE (10 mg/kg, i.p.) failed to change NGF mRNA levels in neonatal rats, while increasing (2-3-fold) NGF mRNA levels in the cerebral cortex of adult rats. In 24-month-old rats, both DEX and CLE elicited only a modest increase in NGF mRNA. This increase was, however, anatomically and temporally similar to that observed in adult animals. The weak effect of DEX or CLE was not related to a down-regulation of receptor function because both DEX and CLE were able to elicit a comparable increase in the mRNA levels for basic fibroblast growth factor (FGF2) in neonatal, adult and aged rat brain. Our data demonstrate that induction of NGF expression by neurotransmitter/hormone receptor activation varies throughout life and suggest that pharmacological agents might be useful tools to enhance trophic support in aging.
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Encéfalo/metabolismo , Factor 2 de Crecimiento de Fibroblastos/biosíntesis , Regulación del Desarrollo de la Expresión Génica , Factores de Crecimiento Nervioso/biosíntesis , Transcripción Genética , Agonistas Adrenérgicos beta/farmacología , Envejecimiento , Animales , Animales Recién Nacidos , Encéfalo/efectos de los fármacos , Encéfalo/crecimiento & desarrollo , Cerebelo/metabolismo , Corteza Cerebral/metabolismo , Clenbuterol/farmacología , Cuerpo Estriado/metabolismo , Dexametasona/farmacología , Regulación del Desarrollo de la Expresión Génica/efectos de los fármacos , Hipocampo/metabolismo , Hipotálamo/metabolismo , Masculino , Especificidad de Órganos , ARN Mensajero/biosíntesis , Ratas , Ratas Endogámicas F344 , Ratas Sprague-Dawley , Transcripción Genética/efectos de los fármacosRESUMEN
1. Male and female broiler chickens (144 in total) were given diets supplemented with clenbuterol (CB) at 0 (control) and at 1 mg/kg between 28 and 49 d of age to study the effect of CB on growth, carcase and skeletal muscle. 2. CB improved growth in males by increasing daily weight gain and final live weight and by lowering food conversion ratio. In females it changed the carcase composition by reducing abdominal fat pad and by increasing the proportion of protein. Consequently, carcase protein gain was increased in both sexes (11% and 16%, respectively). 3. Skeletal muscle weights were enhanced by between 6% and 22%. Muscle fibre diameters were increased in extensor hallucis longus (EHL) but not in gastrocnemius (GAS) muscle. This increase was more pronounced in females. EHL total muscle fibre number remained unchanged. The proportion of fast-twitch glycolytic fibres was increased at the expense of fast-twitch oxidative fibres in males only. Nuclear/cytoplasm and DNA/protein ratios tended to be decreased by CB. 4. From the elevated EHL muscle RNA/DNA, unchanged protein/RNA and translation activity it is suggested that CB stimulated protein synthesis at the pretranslational level. Reduced protein degradation is deduced from decreased neutral calcium-dependent proteolytic activity. 5. It is concluded that broiler chickens respond to long-term CB treatment as has been shown in various mammals. However, the sex-specific response in growth, carcase composition and skeletal muscle cellularity is more clearly apparent in broiler chickens.
Asunto(s)
Agonistas Adrenérgicos beta/farmacología , Clenbuterol/farmacología , Carne/normas , Músculo Esquelético/efectos de los fármacos , Agonistas Adrenérgicos beta/administración & dosificación , Animales , Pollos , Clenbuterol/administración & dosificación , ADN/metabolismo , Suplementos Dietéticos , Femenino , Masculino , Desarrollo de Músculos , Fibras Musculares Esqueléticas/citología , Fibras Musculares Esqueléticas/efectos de los fármacos , Fibras Musculares Esqueléticas/fisiología , Proteínas Musculares/biosíntesis , Músculo Esquelético/anatomía & histología , Músculo Esquelético/crecimiento & desarrollo , Tamaño de los Órganos , Biosíntesis de Proteínas , ARN/metabolismo , Caracteres Sexuales , Aumento de Peso/efectos de los fármacosRESUMEN
The goal of this experiment was to determine whether modulation of beta 2-adrenoceptors influenced DMI of lactating dairy cows. Because stimulation of these receptors induces mobilization of body fat stores, the effect of such stimulation on feed intake was compared with the effect of an intravenous administration of lipid nutrients. Four treatments were infused intravenously over a 4-h period: 1) a beta 2-agonist (clenbuterol), 2) a beta-blocker (propranolol), 3) triglyceride emulsion (lipids), or 4) saline. Two trials were carried out for the same four cows to compare the effects of two expected lipolytic situations. Trial 1 used cows at 60 DIM treated with infusions from 0300 to 0700 h, and trial 2 used cows at 92 DIM treated with infusions from 0800 to 1200 h. Each trial was composed of three consecutive replications of a 4 x 4 balanced Latin square design with 2-d periods. A complete diet (70% maize silage and 30% concentrate) was offered for ad libitum intake. In both trials, clenbuterol reduced DMI on the day of infusion (-7.9 and -11.2% for trials 1 and 2, respectively) and on the following day (-5.1 and -6.3% in trials 1 and 2, respectively). This decrease occurred some time after the end of infusion. Intravenous lipid supplementation reduced DMI during infusion in both trials and during the entire day in trial 2. Both clenbuterol and lipids increased plasma NEFA only during infusion. Propranolol had no effect on DMI or basal lipolysis. The data demonstrated that stimulating beta 2-adrenoceptors reduced DMI but in a manner different from that of lipid energy supplementation.
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Bovinos/fisiología , Ingestión de Alimentos/fisiología , Emulsiones Grasas Intravenosas/farmacología , Metabolismo de los Lípidos , Receptores Adrenérgicos beta/fisiología , Agonistas Adrenérgicos beta/farmacología , Antagonistas Adrenérgicos beta/farmacología , Animales , Clenbuterol/farmacología , Ácidos Grasos no Esterificados/sangre , Femenino , Cinética , Lactancia , Lipólisis , Propranolol/farmacología , Receptores Adrenérgicos beta/efectos de los fármacosRESUMEN
Basal and electrical stimulation-induced release of tritiated norepinephrine (3H-NE) was determined in superfused slices of the rat hypothalamus and hippocampus. Isoproterenol (0.1-10 nM), a nonselective beta-adrenergic agonist, enhanced stimulation-evoked release of 3H-NE from hypothalamic and hippocampal slices in a concentration-dependent manner without consistently altering basal release. Isoproterenol (1 nM) increased ratios of S2/S1 to 143 +/- 4% (hypothalamus) and 152 +/- 15% (hippocampus) of control values. The facilitatory effects of isoproterenol were antagonized by propranolol (50 nM), a nonselective beta-adrenergic antagonist. The beta 2-selective adrenergic agonist clenbuterol (10-100 microM) enhanced basal release of 3H-NE in a concentration-dependent fashion. These results provide evidence for a beta-adrenergic receptor mediated regulation of NE release from hypothalamic and hippocampal slices. Whether the positive feedback mechanism contributes to any of the NE-mediated physiological functions associated with the hypothalamus and hippocampus requires further study. However, the effect of clenbuterol indicates that some of its behavioral actions in animals may be attributed to this NE release-enhancing effect observed in the present study.
Asunto(s)
Hipocampo/metabolismo , Hipocampo/ultraestructura , Hipotálamo/metabolismo , Hipotálamo/ultraestructura , Norepinefrina/metabolismo , Receptores Adrenérgicos beta/fisiología , Agonistas de Receptores Adrenérgicos beta 2 , Agonistas Adrenérgicos beta/farmacología , Antagonistas Adrenérgicos beta/farmacología , Animales , Clenbuterol/farmacología , Estimulación Eléctrica , Hipocampo/efectos de los fármacos , Hipotálamo/efectos de los fármacos , Técnicas In Vitro , Isoproterenol/antagonistas & inhibidores , Isoproterenol/farmacología , Masculino , Propranolol/farmacología , Ratas , Ratas Sprague-Dawley , Receptores Adrenérgicos beta/efectos de los fármacos , TritioRESUMEN
We examined the role of IGF-I in muscle growth stimulated by a beta-adrenergic agonist, clenbuterol. Ewe lambs (90 d old, 20.4 kg mean live weight) were allotted to five groups. A pretreatment control group of five lambs was slaughtered immediately (0 d). The other four groups of six ewes ate freely for 38 or 80 d and were then slaughtered. Half those lambs received clenbuterol (400 micrograms.kg live weight-1.d-1) as a dietary supplement. Blood was collected at intervals from 19 d before supplementation began (0 d) until slaughter. Prerigor muscle samples were sectioned for detection of IGF-I receptors and myofibrillar ATPase activity. Carcass weights were slightly increased by treatment, whereas muscle weights (semimembranosus, gastrocnemius, and biceps femoris) were greatly increased (P < .001), up to 48% at 80 d for semimembranosus. Clenbuterol significantly decreased collagen concentration because myofibrillar proteins were preferentially produced. Collagen solubility was unaffected. Total RNA:total DNA in semimembranosus and gastrocnemius showed transcription was still stimulated between 38 and 80 d. Fiber type area analysis indicated a shift toward glycolytic metabolism, confirmed by iron measurements. However, clenbuterol did not change the portion of muscle occupied by each ATPase class, and the data indicated that type I fibers, though smaller, became relatively more numerous. In spite of significant muscle changes, plasma IGF-I was unaffected by clenbuterol. Similarly, there was no difference in the specific binding of [125I]IGF-I at slaughter between treated and control lambs. However, a response in the first few days of treatment, preceding visible hypertrophy, cannot be excluded.
Asunto(s)
Agonistas Adrenérgicos beta/farmacología , Clenbuterol/farmacología , Factor I del Crecimiento Similar a la Insulina/fisiología , Ovinos/crecimiento & desarrollo , Agonistas Adrenérgicos beta/administración & dosificación , Animales , Clenbuterol/administración & dosificación , Colágeno/análisis , ADN/análisis , Femenino , Alimentos Fortificados , Factor I del Crecimiento Similar a la Insulina/análisis , Radioisótopos de Yodo , Carne/normas , Fibras Musculares Esqueléticas/química , Fibras Musculares Esqueléticas/ultraestructura , Músculo Esquelético/anatomía & histología , Músculo Esquelético/química , Músculo Esquelético/efectos de los fármacos , Tamaño de los Órganos/fisiología , ARN/análisis , Distribución Aleatoria , Ovinos/fisiología , Factores de TiempoRESUMEN
1. Ducks (622 in total) aged 25 d were given diets supplemented with clenbuterol (CL) at 0 (control), 0.5, 1, 2, 3 and 5 mg/kg for 25 d to investigate the effect of dietary CL on muscle and fat deposition and some metabolites in ducks. 2. The mass of the breast muscles was increased by 10 to 31%, while subcutaneous fat plus skin and abdominal fat pad were reduced by 8 to 23% and 20 to 37%, respectively, in the ducks supplemented 1 to 5 mg CL/kg diet. 3. Increased RNA:DNA ratios in the breast muscle, reduced uric acid and increased free fatty acid concentrations in the serum were observed in clenbuterol-fed ducks.
Asunto(s)
Clenbuterol/farmacología , Alimentos Fortificados , Carne , Músculos/efectos de los fármacos , Tejido Adiposo/anatomía & histología , Tejido Adiposo/efectos de los fármacos , Tejido Adiposo/metabolismo , Alimentación Animal , Animales , Clenbuterol/administración & dosificación , ADN/metabolismo , Patos , Ácidos Grasos no Esterificados/sangre , Músculos/anatomía & histología , Músculos/metabolismo , ARN/metabolismo , Valores de Referencia , Ácido Úrico/sangreRESUMEN
The effects of chronic postnatal beta 2-adrenoceptor activation on the maturation of the rat brain noradrenergic system have been studied. For that purpose, rat pups have been treated twice daily during the first 10 days of life with the beta 2-agonist clenbuterol-HCl (2.5 mg/kg s.c.), and the effects on the beta-adrenoceptor number and monoamine metabolism have been determined directly after the treatment and in adulthood. On postnatal day 10, 90 min after the last clenbuterol injection 4.5 micrograms/g of the drug was present in the brain. At the end of the treatment the beta-receptor binding had decreased in the cerebellum (35%), but not in the frontal cortex or mesolimbic system. Clenbuterol significantly increased the steady-state brain levels of noradrenaline (NA) in the striatum 90 min after the last injection, whereas the levels in the frontal cortex, meso-limbic system, medulla pons and cerebellum were unaffected. The NA metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG), had significantly increased in the frontal cortex and striatum. The serotonergic (5-HT) and dopaminergic (DA) system were not altered. In general, no long-lasting effects on beta-adrenoceptor number and affinity or monoamine metabolism were measurable, except for the frontal cortex which showed a sustained increase of MHPG, a decrease of 5-HT and an increase of 5-HIAA/5-HT on PN 60. In conclusion, chronic postnatal activation of beta 2-adrenoceptors by clenbuterol treatment selectively causes changes in the setting of the neurochemical parameters investigated in the frontal cortex.
Asunto(s)
Envejecimiento/fisiología , Encéfalo/metabolismo , Clenbuterol/farmacología , Dopamina/metabolismo , Norepinefrina/metabolismo , Receptores Adrenérgicos beta/metabolismo , Serotonina/metabolismo , Ácido 3,4-Dihidroxifenilacético/metabolismo , Animales , Animales Recién Nacidos , Encéfalo/efectos de los fármacos , Cerebelo/efectos de los fármacos , Cerebelo/metabolismo , Esquema de Medicación , Lóbulo Frontal/efectos de los fármacos , Lóbulo Frontal/metabolismo , Ácido Homovanílico/metabolismo , Ácido Hidroxiindolacético/metabolismo , Radioisótopos de Yodo , Yodocianopindolol , Sistema Límbico/efectos de los fármacos , Sistema Límbico/metabolismo , Masculino , Metoxihidroxifenilglicol/metabolismo , Especificidad de Órganos , Pindolol/análogos & derivados , Pindolol/metabolismo , Ratas , Ratas Wistar , Receptores Adrenérgicos beta/efectos de los fármacos , Valores de ReferenciaAsunto(s)
Adyuvantes Inmunológicos/farmacología , Vacuna BCG/farmacología , Clenbuterol/farmacología , Hematopoyesis/efectos de los fármacos , Leucemia Experimental/tratamiento farmacológico , Virus Rauscher , Suramina/farmacología , Adyuvantes Inmunológicos/uso terapéutico , Animales , Vacuna BCG/uso terapéutico , Médula Ósea/efectos de los fármacos , Clenbuterol/uso terapéutico , Evaluación Preclínica de Medicamentos , Femenino , Leucemia Experimental/sangre , Masculino , Ratones , Ratones Endogámicos BALB C , Suramina/uso terapéutico , Factores de TiempoRESUMEN
Treatment of tumor-bearing (TB) and control rats with the anabolic beta-2 agonist drug clenbuterol (CLE) for 14 days reduced food intake for 4 days initially. Feeding was increased in anorectic TB rats, however, during the last 7 days of drug administration. Since minimal muscle savings were observed in chow-fed TB rats treated with CLE, the anabolic effects of this drug were investigated in a second experiment on TB rats maintained on total parenteral nutrition (TPN). Sixteen days after the subcutaneous transplantation of methylcholanthrene-induced sarcomas rats was begun on a 2-week schedule of TPN. One group of these rats was treated daily for 14 days with CLE, while the remaining rats received injections of saline. Additional groups of TB and nonTB rats were maintained on rat chow for this period and treated with saline. Although TB rats maintained on rat chow or TPN and treated with saline exhibited significantly decreased gastrocnemius muscle weight and protein content, treatment of TB-TPN rats with clenbuterol normalized muscle mass and increased muscle protein content significantly and increased plasma concentrations of branched-chain amino acids. These results indicate that although nutritional support of TB organisms does not result in protein repletion, the addition of an anabolic drug renders the nutritional support highly efficacious.
Asunto(s)
Clenbuterol/farmacología , Nutrición Parenteral Total , Sarcoma Experimental/terapia , Animales , Caquexia/metabolismo , Caquexia/patología , Caquexia/terapia , Terapia Combinada , Masculino , Músculos/efectos de los fármacos , Músculos/patología , Proteínas de Neoplasias/metabolismo , Ratas , Ratas Endogámicas F344 , Sarcoma Experimental/metabolismo , Sarcoma Experimental/patologíaRESUMEN
A non-invasive radio-aerosol technique was employed to study mucociliary clearance patterns in three groups of four calves of different ages. The initial clearance pattern, the percentage cleared in 1 h, and the percentage cleared between 1 and 19 h were used as indices of clearance efficiency. (Percentage retention at 19 h was used as an index of alveolar deposition.) These measurements were recorded in a series of experiments designed to investigate the effects of: clenbuterol (given as a single intravenous injection, 0.75 microgram/kg); a combination of trimethoprim and sulphadiazine-TMPS (administered by intramuscular injection twice daily for 3 days: 2.5 mg/kg trimethoprim; 12.5 mg/kg sulphadiazine) alone, or with a supplementary injection of clenbuterol; and oxytetracycline (administered by intramuscular injection twice daily for 3 days; 3 mg/kg). Clenbuterol alone tended to increase clearance rate, although this effect did not achieve statistical significance. The combination of TMPS with clenbuterol produced results similar to those of clenbuterol alone. Neither TMPS nor oxytetracycline had any significant effect on indices of mucociliary clearance. Differences were observed between calves of different age groups, particularly in clearance phases between 1 and 19 h.
Asunto(s)
Antiinfecciosos/farmacología , Bovinos/fisiología , Clenbuterol/farmacología , Etanolaminas/farmacología , Depuración Mucociliar/efectos de los fármacos , Administración por Inhalación , Aerosoles , Animales , Combinación de Medicamentos , Oxitetraciclina/farmacología , Sulfadiazina/farmacología , Trimetoprim/farmacologíaRESUMEN
The effects of intraperitoneal administration of isoproterenol (a mixed beta 1- and beta 2-agonist), dobutamine (a selective beta 1-agonist) and clenbuterol (a selective beta 2-agonist) on gastric emptying were investigated in mice killed 30 min after gavage with a 51Cr radiolabeled milk meal. Administered 30 min prior to the meal, isoproterenol (2 mg/kg) and dobutamine (1 and 2 mg/kg) accelerated gastric emptying and clenbuterol (0.05 and 0.1 mg/kg) slowed it. The stimulation of gastric emptying by isoproterenol (2 mg/kg) and dobutamine (2 mg/kg) was blocked by the previous administration of either mixed beta 1- and beta 2-antagonist, propranolol (1 mg/kg), or a specific beta 1-antagonist, acebutolol (1 mg/kg). Only propranolol (1 mg/kg) antagonized the decrease of gastric emptying induced by clenbuterol. A high dose of propranolol (10 mg/kg), injected alone, reduced gastric emptying. It is concluded that the increase in gastric emptying caused by beta-adrenergic drugs is mediated through beta 1-adrenoceptors, while beta 2-receptors are involved in the inhibition of this function. The lack of effects of propranolol at doses able to block the action of beta 1- and beta 2-adrenoceptor agonists suggests that beta-adrenoceptors are not physiologically involved in the control of gastric emptying.
Asunto(s)
Grasas de la Dieta/administración & dosificación , Vaciamiento Gástrico/efectos de los fármacos , Receptores Adrenérgicos beta/fisiología , Acebutolol/farmacología , Animales , Radioisótopos de Cromo , Clenbuterol/farmacología , Dobutamina/farmacología , Isoproterenol/farmacología , Masculino , Ratones , Propranolol/farmacologíaRESUMEN
The reduction of food intake in hungry rats induced by salbutamol (10 mg/kg/i.p.) was prevented by IPS 339 (5 mg/kg, i.p.) a selective beta 2 adrenergic antagonist, but not by metoprolol (10 mg/kg i.p.), a blocker of beta 1 adrenergic receptors. Similarly, bilateral injections of IPS 339 (32 micrograms/1 microliter) but not metoprolol (80 micrograms/1 microliter) in the perifornical hypothalamic area completely antagonized the anorectic effect of intraperitoneal salbutamol, suggesting an involvement of beta 2 adrenergic receptors in this brain area. Clenbuterol, a beta 2 adrenergic agonist which readily crosses the blood-brain barrier, was 10-100 times more potent than salbutamol in inhibiting feeding consumption of deprived rats when injected intraperitoneally and this effect was also selectively antagonized by pretreatment with IPS 339. Neither IPS 339 nor metoprolol injected in the perifornical hypothalamus significantly modified the anorectic effect of diethylpropion (5 mg/kg i.p.) whereas it was partially prevented by intraperifornical injection of 1-propranolol (52 micrograms/2 microliter), a non-selective beta antagonist, suggesting that both beta 1 and beta 2 adrenergic receptors in the hypothalamus contribute to the mechanism by which diethylpropion causes anorexia.