RESUMEN
Aging is associated with oxidative damage and an imbalance in redox signaling in a variety of tissues, yet little is known about the extent of age-induced oxidative stress in the sympathoadrenal system. Lifelong caloric restriction has been shown to lower levels of oxidative stress and slow the aging process. Therefore, the aims of this study were twofold: (1) to investigate the effect of aging on oxidative stress in the adrenal medulla and hypothalamus and (2) determine if lifelong 40% caloric restriction (CR) reverses the adverse effects of age-induced oxidative stress in the sympathetic adrenomedullary system. Adult (18months) and very old (38months) male Fischer 344 x Brown Norway rats were divided into ad libitum or 40% CR groups and parameters of oxidative stress were analyzed in the adrenal medulla and the hypothalamus. A significant age-dependent increase in lipid peroxidation (+20%, P<0.05) and tyrosine nitration (+111%, P<0.001) were observed in the adrenal medulla while age resulted in a reduction in the protein expression of key antioxidant enzymes, CuZnSOD (-27%, P<0.01) and catalase (-27%, P<0.05) in the hypothalamus. Lifelong CR completely prevented the age-induced increase in lipid peroxidation in the adrenal medulla and restored the age-related decline in antioxidant enzymes in the hypothalamus. These data indicate that aging results in a significant increase in oxidative stress in the sympathoadrenal system. Importantly, lifelong CR restored the age-related changes in oxidative stress in the adrenal medulla and hypothalamus. Caloric restriction could be a potential non-pharmacological intervention to prevent increased oxidative stress in the sympathetic adrenomedullary system with age.
Asunto(s)
Médula Suprarrenal/fisiología , Envejecimiento/fisiología , Restricción Calórica , Hipotálamo/fisiología , Estrés Oxidativo , Sistema Nervioso Simpático/fisiología , Médula Suprarrenal/enzimología , Factores de Edad , Aldehídos/metabolismo , Animales , Peso Corporal , Hipotálamo/enzimología , Ratas , Ratas Endogámicas BN , Ratas Endogámicas F344 , Superóxido Dismutasa/biosíntesisRESUMEN
This paper gives an account of the functioning of the two systems in different stress induced situations. The activation of the sympathetic-adrenal medullary system is accompanied by the release of catecholamines, while the increased activity of the hypothalamic-pituitary-adrenal system results in the increased release of corticosteroids, especially cortisol. The role of the sympathetic-adrenal medullary system was investigated in immunologic changes induced by laboratory stressors. In the real, as in laboratory conditions, the effects of different stressors on the level of cortisol were studied, as it is the final product of the hypothalamic-pituitary-adrenal system activity. Additional (negative) effects on the functioning of these systems could induce some variables, as an increased consumption of alcohol, smoking, and sleeping disorder. Furthermore, the methodological shortcomings and the selection of subjects in previous studies are discussed. Previous results are also discussed, such as the immunosuppressive effects of cortisol, as well as the mediator and moderator variables in relation to stress and immunoreactivity.
Asunto(s)
Médula Suprarrenal/fisiología , Sistema Hipotálamo-Hipofisario/fisiología , Inmunidad/fisiología , Sistema Hipófiso-Suprarrenal/fisiología , Estrés Psicológico/inmunología , Estrés Psicológico/fisiopatología , Humanos , PsiconeuroinmunologíaRESUMEN
To investigate the influence of medullary adrenal secretion on thermoregulation during exercise, Phy (Eserine, 5x10(-3) M) was injected into the lateral cerebral ventricle of normal (INT) or bilaterally adrenodemedullated (ADM) untrained rats. Body temperature (Tb) and metabolic rate were measured in the rats while they were exercising on a treadmill (20 m min(-1), 5% inclination) until fatigue or while they were at rest after drug injection. In resting rats, Phy increased oxygen consumption in both INT or ADM rats without any effect on core temperature. During the dynamic phase of exercise (first 20 min), ADM attenuated the exercise-induced increase in core temperature (0.86+/-0.12 degrees C ADM Sal vs 1.48+/-0.21 degrees C INT Sal), thus reducing heat storage (HS) levels. Icv injection of Phy in ADM rats significantly reduced the increase in Tb (0.012+/-0.10 degrees C min(-1) Phy vs 0.042+/-0.006 degrees C min(-1) Sal; p<0.02) and HS (65.8+/-56.1 cal Phy vs 207.7+/-32.7 cal Sal; p<0.04) compared to ADM Sal rats. In conclusion, the exercise-induced increase in heat storage was attenuated by adrenodemedullation in rats. Furthermore, the activation of heat loss mechanisms by the central cholinergic system during exercise occurs independently of adrenal medullary secretion suppression and can be improved by previous adrenodemedullation. Our data indicate the existence of a dual mechanism of heat loss control during the dynamic phase of exercise: one involving sympathoadrenal system activation that impairs heat loss and another that counteracts the increased sympathoadrenal activity through the hypothalamic cholinergic system to promote heat loss.
Asunto(s)
Médula Suprarrenal/fisiología , Temperatura Corporal/fisiología , Consumo de Oxígeno/fisiología , Condicionamiento Físico Animal/métodos , Adrenalectomía/métodos , Animales , Conducta Animal , Temperatura Corporal/efectos de los fármacos , Inhibidores de la Colinesterasa/farmacología , Metabolismo Energético/efectos de los fármacos , Metabolismo Energético/fisiología , Hipotálamo/efectos de los fármacos , Hipotálamo/fisiología , Inyecciones Intraventriculares/métodos , Masculino , Consumo de Oxígeno/efectos de los fármacos , Fisostigmina/farmacología , Ratas , Ratas WistarRESUMEN
Although the frequency-dependent antinociceptive mechanisms of electroacupuncture (EA) have been well demonstrated, the anti-inflammatory mechanisms that underlie the suppressive effects induced by different frequencies of EA stimulation on peripheral inflammation are largely unknown. We have previously reported that EA stimulation can activate the sympathetic nervous system (SNS) and that this activation is responsible for the EA-induced suppression of zymosan-induced leukocyte migration. The present study was designed to evaluate the differential effect of low (1Hz, LF EA) versus high (120Hz, HF EA) frequency EA stimulation on SNS activation and ultimately on carrageenan-induced inflammation. Immediately after carrageenan injection, we applied either LF EA or HF EA bilaterally to the Zusanli (ST36) acupoints. To evaluate the anti-inflammatory effect of EA (EA-AI), paw volume and myeloperoxidase (MPO) activity, a marker of infiltrated leukocytes, were measured and the paw withdrawal latency to noxious heat stimulation was also assessed. Both LF EA and HF EA significantly suppressed the carrageenan-induced paw edema and MPO activity. Moreover, thermal hyperalgesia was strongly attenuated in both the LF EA and HF EA groups. Adrenalectomy significantly diminished HF EA-AI without affecting LF EA-AI. Pretreatment with the corticosterone receptor antagonist, RU-486 did not affect either LF EA- or HF EA-AI. On the other hand, administration of 6-hydroxydopamine (a neurotoxin for peripheral sympathetic nerve endings) selectively blocked LF EA-AI. Propranolol (a beta-adrenoceptor antagonist) completely abolished both LF EA- and HF EA-AI. The results of this study suggest that the suppressive effects of LF EA on carrageenan-induced paw inflammation are mediated by sympathetic post-ganglionic neurons, while the suppressive effects of HF EA are mediated by the sympatho-adrenal medullary axis.
Asunto(s)
Médula Suprarrenal/fisiología , Estimulación Eléctrica/métodos , Electroacupuntura/métodos , Ganglios Simpáticos/patología , Inflamación/patología , Inflamación/terapia , Neuronas/efectos de la radiación , Médula Suprarrenal/efectos de la radiación , Adrenalectomía , Adrenérgicos/administración & dosificación , Animales , Carragenina , Modelos Animales de Enfermedad , Relación Dosis-Respuesta en la Radiación , Edema/inducido químicamente , Edema/patología , Antagonistas de Hormonas/administración & dosificación , Inflamación/inducido químicamente , Masculino , Ratones , Ratones Endogámicos ICR , Mifepristona/administración & dosificación , Neuronas/fisiología , Umbral del Dolor/efectos de los fármacos , Umbral del Dolor/fisiología , Umbral del Dolor/efectos de la radiación , Peroxidasa/metabolismo , Factores de TiempoRESUMEN
The present study was conducted to evaluate the contribution of endothelin (ET) to the pharmacodynamic response to chronic cigarette smoke in spontaneously hypertensive rats (SHR). The contribution of ET was studied consequent to the hemodynamic response following 8 weeks of cigarette smoke by determining the changes in tissue ET-1 content and ET receptors. The blood pressure (BP) at the early phase of smoking and the heart rate (HR) 24 h later were apparently reduced in SHR, while the HR at the early phase was transiently elevated in normotensive Wistar Kyoto (WKY) rats. Tissue ET-1 levels in the hypothalamus, striatum, and cortex of SHR were higher than those in WKY rats, and these higher levels in SHR were reduced by exposure to chronic cigarette smoke. The ET-1 contents in the medulla oblongata and midbrain of both strains were clearly increased by smoke exposure, although the levels of SHR and WKY rats were not different. In addition, the immunoreactivity of the ET type A receptor in the adrenal glands and type B receptor in the kidneys of SHR showed a different response to smoke exposure as compared to WKY rats. Our present findings suggest that the changes of ETs may relate to the pharmacodynamic effects of chronic cigarette smoke.
Asunto(s)
Química Encefálica/fisiología , Endotelinas/fisiología , Nicotiana/efectos adversos , Receptor de Endotelina A/metabolismo , Receptor de Endotelina B/metabolismo , Fumar/fisiopatología , Médula Suprarrenal/efectos de los fármacos , Médula Suprarrenal/fisiología , Médula Suprarrenal/ultraestructura , Animales , Presión Sanguínea/efectos de los fármacos , Química Encefálica/efectos de los fármacos , Evaluación Preclínica de Medicamentos/métodos , Endotelinas/efectos de los fármacos , Corazón/efectos de los fármacos , Corazón/fisiología , Frecuencia Cardíaca/efectos de los fármacos , Riñón/efectos de los fármacos , Riñón/fisiología , Masculino , Ratas , Ratas Endogámicas SHR , Ratas Endogámicas WKY , Receptor de Endotelina A/efectos de los fármacos , Receptor de Endotelina A/genética , Receptor de Endotelina B/efectos de los fármacos , Receptor de Endotelina B/genética , Humo/efectos adversos , Fumar/efectos adversos , Factores de TiempoRESUMEN
BACKGROUND: Fasting and diabetes are characterized by elevated glucocorticoids and reduced insulin, leptin, elevated hypothalamic AGRP and NPY mRNA, and reduced hypothalamic POMC mRNA. Although leptin replacement can reverse changes in hypothalamic gene expression associated with fasting and diabetes, leptin also normalizes corticosterone; therefore the extent to which the elevated corticosterone contributes to the regulation of hypothalamic gene expression in fasting and diabetes remains unclear. To address if elevated corticosterone is necessary for hypothalamic responses to fasting and diabetes, we assessed the effects of adrenalectomy on hypothalamic gene expression in 48-hour-fasted or diabetic mice. To assess if elevated corticosterone is sufficient for the hypothalamic responses to fasting and diabetes, we assessed the effect of corticosterone pellets implanted for 48 hours on hypothalamic gene expression. RESULTS: Fasting and streptozotocin-induced diabetes elevated plasma glucocorticoid levels and reduced serum insulin and leptin levels. Adrenalectomy prevented the rise in plasma glucocorticoids associated with fasting and diabetes, but not the associated reductions in insulin or leptin. Adrenalectomy blocked the effects of fasting and diabetes on hypothalamic AGRP, NPY, and POMC expression. Conversely, corticosterone implants induced both AGRP and POMC mRNA (with a non-significant trend toward induction of NPY mRNA), accompanied by elevated insulin and leptin (with no change in food intake or body weight). CONCLUSION: These data suggest that elevated plasma corticosterone mediate some effects of fasting and diabetes on hypothalamic gene expression. Specifically, elevated plasma corticosterone is necessary for the induction of NPY mRNA with fasting and diabetes; since corticosterone implants only produced a non-significant trend in NPY mRNA, it remains uncertain if a rise in corticosterone may be sufficient to induce NPY mRNA. A rise in corticosterone is necessary to reduce hypothalamic POMC mRNA with fasting and diabetes, but not sufficient for the reduction of hypothalamic POMC mRNA. Finally, elevated plasma corticosterone is both necessary and sufficient for the induction of hypothalamic AGRP mRNA with fasting and diabetes.
Asunto(s)
Diabetes Mellitus Experimental/fisiopatología , Ayuno/fisiología , Regulación de la Expresión Génica/fisiología , Glucocorticoides/fisiología , Hipotálamo/fisiología , Hipotálamo/fisiopatología , Médula Suprarrenal/fisiología , Médula Suprarrenal/fisiopatología , Médula Suprarrenal/cirugía , Adrenalectomía/métodos , Proteína Relacionada con Agouti , Animales , Corticosterona/administración & dosificación , Corticosterona/farmacología , Diabetes Mellitus Experimental/sangre , Implantes de Medicamentos/farmacología , Regulación de la Expresión Génica/efectos de los fármacos , Glucocorticoides/sangre , Hipotálamo/efectos de los fármacos , Insulina/deficiencia , Insulina/genética , Insulina/fisiología , Péptidos y Proteínas de Señalización Intercelular , Leptina/genética , Masculino , Ratones , Ratones Endogámicos C57BL , Neuropéptido Y/genética , Proopiomelanocortina/genética , Proteínas/genética , ARN Mensajero/genética , ARN Mensajero/metabolismoRESUMEN
Green tea contains four major polyphenol compounds: they are (-)-epigallocatechin-3-gallate (EGCG), (-)-epigallocatechin (EGC), (-)-epicatechin-3-gallate (ECG), and (-)-epicatechin (EC). Although all four polyphenol compounds are known to affect tumor suppression, little is known about whether they alter membrane properties. In this study, we examined the effects of ECG and EGCG on ionic currents and secretion. Membrane capacitance changes were used to monitor secretion in bovine chromaffin cells. ECG had the ability to reversibly enhance the inward Ca(2+) current by 21%, and inhibited the peak sodium current by 34%. EGCG had no effect on Ca(2+) current even though it differs from ECG by just a hydroxyl group. The EC(50) of ECG in enhancing Ca(2+) current was 7.6 microM. The maximum enhancement of Ca(2+) current was observed at 0 mV and the maximum current was shifted approximately 10 mV in the hyperpolarizing direction. When cells were stimulated by trains of depolarizations, the exocytosis elicited was enhanced by ECG treatment and the largest enhancement of secretion was observed in later stimulations. EGCG, although it had no significant effect on Ca(2+) current, enhanced exocytosis and slowed endocytosis. These results suggest that green tea polyphenol compounds modulate stimulus-secretion coupling in bovine chromaffin cells.
Asunto(s)
Antioxidantes/farmacología , Señalización del Calcio/fisiología , Catequina/farmacología , Células Cromafines/fisiología , Flavonoides , Fenoles/farmacología , Extractos Vegetales/farmacología , Polímeros/farmacología , Médula Suprarrenal/fisiología , Animales , Señalización del Calcio/efectos de los fármacos , Catequina/análogos & derivados , Bovinos , Células Cromafines/efectos de los fármacos , Técnicas In Vitro , Cinética , Potenciales de la Membrana/efectos de los fármacos , Potenciales de la Membrana/fisiología , Técnicas de Placa-Clamp , Factores de TiempoRESUMEN
With the aim of evaluating the sympathetic-adrenal medulla system in subjects practicing transcendental meditation (TM), their plasma catecholamine levels were determined at two different times of day. The study group consisted of 19 subjects who regularly practice either TM or Sidhi-TM technique, with a control group made up of 16 healthy subjects who had not previously used any relaxation technique. Catecholamine plasma levels were determined by high performance liquid chromatography, at 0900 and 2000 h. Morning and evening norepinephrine (NE) levels and morning epinephrine (E) levels were significantly lower in the TM group than in the control subjects (morning NE levels, pg/ml, mean+/-S.E.: TM group 136.6+/-13.0, control 236.8+/-21.0, P=.0001; evening NE levels: TM group 119.7+/-10.8, control 175.6+/-17.4, P=.009; morning E levels, pg/ml: TM group 140.2+/-10.6, control 196.7+/-23.8, P=.019). No differences were recorded for evening E levels and dopamine (DA) levels. No significant differences were found for catecholamine levels measured at different times of day in the TM group, demonstrating a lack of daily hormonal rhythm. Anxiety levels were similar in both groups. Based on the results obtained, it can be considered that the regular practice of TM has a significant effect on the sympathetic-adrenal medulla system. A low hormonal response to daily stress caused by sympathetic tone regulation through regular TM could explain our results, as well as the physiological and other effects related to the field of health described in those who practice meditation.
Asunto(s)
Catecolaminas/sangre , Meditación/psicología , Adolescente , Médula Suprarrenal/fisiología , Adulto , Cromatografía Líquida de Alta Presión , Ritmo Circadiano/fisiología , Dopamina/sangre , Epinefrina/sangre , Femenino , Humanos , Masculino , Norepinefrina/sangre , Sistema Nervioso Simpático/fisiologíaRESUMEN
The effects of electro-acupuncture stimulation (EAS) of two different areas of a hindlimb with different stimulus intensities on sympathoadrenal medullary functions were examined in anesthetized artificially ventilated rats. Two needles of 160 microm diameter and about 5 mm apart were inserted about 5 mm deep into a hindpaw (Chungyang, S42) or a hind leg (Tsusanli, S36) and current of various intensities passed to excite various afferent nerve fiber groups at a repetition rate of 20 Hz and pulse duration of 0.5 ms for 30-60 s. Fiber groups of afferent nerves stimulated in a hindlimb were monitored by recording evoked action potentials from the afferents innervating the areas stimulated. The sympathoadrenal medullary functions were monitored by recording adrenal sympathetic efferent nerve activity and secretion rates of catecholamines from the adrenal medulla. EAS of a hindpaw at a stimulus strength sufficient to excite the group III and IV somatic afferent fibers produced reflex increases in both adrenal sympathetic efferent nerve activity and the secretion rate of catecholamines. EAS of a hind leg at a stimulus strength sufficient to excite the group III and IV afferent fibers produced reflex responses of either increases or decreases in sympathoadrenal medullary functions. All responses of adrenal sympathetic efferent nerve activity were lost after cutting the afferent nerves ipsilateral to the stimulated areas, indicating that the responses are the reflexes whose afferents nerve pathway is composed of hindlimb somatic nerves. It is concluded that electro-acupuncture stimulation of a hindpaw causes an excitatory reflex, while that of a hind leg causes either excitatory or inhibitory reflex of sympathoadrenal medullary functions, even if both group III and IV somatic afferent fibers are stimulated.
Asunto(s)
Médula Suprarrenal/fisiología , Electroacupuntura/métodos , Miembro Posterior , Reflejo/fisiología , Sistema Nervioso Simpático/fisiología , Potenciales de Acción/fisiología , Vías Aferentes/fisiología , Animales , Masculino , Fibras Nerviosas/fisiología , Ratas , Ratas WistarRESUMEN
Our previous study demonstrated that microinjection of leptin into the ventromedial hypothalamus (VMH) dramatically increased glucose uptake in the heart, brown adipose tissue (BAT), and skeletal muscles, but not in white adipose tissue (WAT) in conscious unrestrained rats, as assessed in vivo by the 2-[3H]deoxyglucose method. Here we examined the role of the sympathetic nervous system and insulin in enhanced glucose uptake by tissues after hypothalamic leptin injection. Pretreatment with guanethidine significantly suppressed the increased glucose uptake by the tissues in response to leptin injected into the VMH, whereas bilateral adrenal demedullation had no significant effect. Treatment with propranolol but not phenoxybenzamine also decreased significantly enhanced glucose uptake by the tissues. We further examined the interaction of the effects of hypothalamic leptin and insulin administered peripherally by clamping the glucose concentrations at a constant level. When leptin was injected into the VMH and a maximal dose of insulin was administered intravenously, the rates of glucose uptake by the heart, BAT, and skeletal muscles, but not by WAT, markedly increased beyond the values reached by insulin stimulation alone. Surgical sympathetic denervation of BAT abolished the enhancement of glucose uptake in this tissue, decreasing to the level stimulated by insulin alone. These results appear to indicate that leptin in the hypothalamus enhances glucose uptake in certain peripheral tissues through mediation of a beta-adrenergic mechanism for the sympathetic nerves innervating the tissues and that central leptin and peripheral insulin have a synergistic role in augmenting tissue glucose uptake.
Asunto(s)
Glucosa/metabolismo , Hipotálamo/efectos de los fármacos , Insulina/fisiología , Proteínas/farmacología , Sistema Nervioso Simpático/efectos de los fármacos , Tejido Adiposo/efectos de los fármacos , Tejido Adiposo/metabolismo , Tejido Adiposo Pardo/efectos de los fármacos , Tejido Adiposo Pardo/metabolismo , Médula Suprarrenal/fisiología , Animales , Guanetidina/farmacología , Corazón/efectos de los fármacos , Leptina , Masculino , Microinyecciones , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/metabolismo , Miocardio/metabolismo , Ratas , Ratas Sprague-DawleyRESUMEN
OBJECTIVE: The author's goal was to develop a pathophysiological model for neuroleptic malignant syndrome with greater explanatory power than the alternative hypotheses of hypothalamic dopamine antagonism (elevated set point) and direct myotoxicity (malignant hyperthermia variant). METHOD: Published clinical findings on neuroleptic malignant syndrome were integrated with data from human and animal studies of muscle physiology, thermoregulation, and autonomic nervous system function. RESULTS: The data show that the sympathetic nervous system's latent capacity for autonomous activity is expressed when tonic inhibitory inputs from higher central nervous system centers are disrupted. These tonic inhibitory inputs are relayed to preganglionic sympathetic neurons by way of dopaminergic hypothalamospinal tracts. The sympathetic nervous system mediates hypothalamic coordination of thermoregulatory activity and is a primary regulator of muscle tone and thermogenesis, augmenting both of these when stimulated. In addition, the sympathetic nervous system modulates all of the other end-organs that function abnormally in neuroleptic malignant syndrome. CONCLUSIONS: There is substantial evidence to support the hypothesis that dysregulated sympathetic nervous system hyperactivity is responsible for most, if not all, features of neuroleptic malignant syndrome. A predisposition to more extreme sympathetic nervous system activation and/or dysfunction in response to emotional or psychological stress may constitute a trait vulnerability for neuroleptic malignant syndrome, which, when coupled with state variables such as acute psychic distress or dopamine receptor antagonism, produces the clinical syndrome of neuroleptic malignant syndrome. This hypothesis provides a more comprehensive explanation for existing clinical data than do the current alternatives.
Asunto(s)
Médula Suprarrenal/fisiología , Antipsicóticos/efectos adversos , Epinefrina/fisiología , Síndrome Neuroléptico Maligno/etiología , Norepinefrina/fisiología , Sistema Nervioso Simpático/fisiología , Médula Suprarrenal/efectos de los fármacos , Médula Suprarrenal/fisiopatología , Antipsicóticos/farmacología , Antipsicóticos/toxicidad , Regulación de la Temperatura Corporal/efectos de los fármacos , Regulación de la Temperatura Corporal/fisiología , Susceptibilidad a Enfermedades/fisiopatología , Hemodinámica/efectos de los fármacos , Hemodinámica/fisiología , Homeostasis/efectos de los fármacos , Homeostasis/fisiología , Humanos , Hipotálamo/efectos de los fármacos , Hipotálamo/fisiología , Hipotálamo/fisiopatología , Modelos Neurológicos , Síndrome Neuroléptico Maligno/fisiopatología , Estrés Psicológico/genética , Estrés Psicológico/fisiopatología , Sistema Nervioso Simpático/efectos de los fármacos , Sistema Nervioso Simpático/fisiopatologíaRESUMEN
Excitation-secretion uncoupling peptides (ESUPs) are inhibitors of Ca2+-dependent exocytosis in neural and endocrine cells. Their mechanism of action, however, remains elusive. We report that ESUP-A, a 20-mer peptide patterned after the C terminus of SNAP-25 (synaptosomal associated protein of 25 kDa) and containing the cleavage sequence for botulinum neurotoxin A (BoNT A), abrogates the slow, ATP-dependent component of the exocytotic pathway, without affecting the fast, ATP-independent, Ca2+-mediated fusion event. Ultrastructural analysis indicates that ESUP-A induces a drastic accumulation of dense-core vesicles near the plasma membrane, mimicking the effect of BoNT A. Together, these findings argue in favor of the notion that ESUP-A inhibits ATP-primed exocytosis by blocking vesicle docking. Identification of blocking peptides which mimic sequences that bind to complementary partner domains on interacting proteins of the exocytotic machinery provides new pharmacological tools to dissect the molecular and mechanistic details of neurosecretion. Our findings may assist in developing ESUPs as substitute drugs to BoNTs for the treatment of spasmodic disorders.
Asunto(s)
Médula Suprarrenal/fisiología , Células Cromafines/fisiología , Gránulos Cromafines/fisiología , Exocitosis/efectos de los fármacos , Proteínas de la Membrana , Proteínas del Tejido Nervioso/fisiología , Norepinefrina/metabolismo , Péptidos/farmacología , Médula Suprarrenal/efectos de los fármacos , Secuencia de Aminoácidos , Animales , Toxinas Botulínicas Tipo A/química , Calcio/farmacología , Bovinos , Permeabilidad de la Membrana Celular , Células Cultivadas , Células Cromafines/efectos de los fármacos , Células Cromafines/ultraestructura , Gránulos Cromafines/efectos de los fármacos , Gránulos Cromafines/ultraestructura , Datos de Secuencia Molecular , Proteínas del Tejido Nervioso/química , Fragmentos de Péptidos , Péptidos/síntesis química , Péptidos/química , Proteína 25 Asociada a SinaptosomasRESUMEN
Intracerebroventricular (i.c.v.) administration of bombesin (0.3 nmol) increased plasma levels of both adrenaline and noradrenaline in urethane anesthetized rats. These bombesin-induced increases were inhibited by i.c.v. pretreatment with pyrilamine, an H1-receptor antagonist. Ranitidine, an H2-receptor antagonist also inhibited the increase of adrenaline, however, its effective dose was much larger than that of pyrilamine. Furthermore, the bombesin-induced increase of noradrenaline was not effectively inhibited by ranitidine. In the next series, turnover of histamine was assessed by measuring accumulation of tele-methylhistamine (t-MH), a major metabolite of brain histamine. I.c.v. administration of bombesin (0.3-3 nmol) increased turnover of hypothalamic histamine, while its intravenous administration was without effect. The present results suggest that the bombesin-induced central activation of sympatho-adrenomedullary outflow is probably, at least in part, mediated through brain histaminergic neurons.
Asunto(s)
Médula Suprarrenal/efectos de los fármacos , Bombesina/farmacología , Encéfalo/metabolismo , Histamina/fisiología , Sistema Nervioso Simpático/efectos de los fármacos , Médula Suprarrenal/fisiología , Animales , Bombesina/administración & dosificación , Epinefrina/sangre , Antagonistas de los Receptores Histamínicos H1/farmacología , Antagonistas de los Receptores H2 de la Histamina/farmacología , Hipotálamo/efectos de los fármacos , Hipotálamo/metabolismo , Inyecciones Intraventriculares , Masculino , Norepinefrina/sangre , Pargilina/farmacología , Pirilamina/farmacología , Ranitidina/farmacología , Ratas , Ratas Wistar , Sistema Nervioso Simpático/fisiologíaRESUMEN
The effects of acupuncture-like stimulation of the abdomen and a hindlimb on the secretion rates of adrenal medullary catecholamine hormones (adrenaline and noradrenaline) and adrenal sympathetic efferent nerve activity were studied using urethane-anesthetized rats. Acupuncture needles (diameter of 340 microns) were inserted into the skin and underlying muscles of either the abdomen or a hindlimb to a depth of 10 mm and then twisted at a frequency of about 1 Hz for 90 s. The stimuli induced three types of response in both catecholamine secretion and adrenal sympathetic nerve activity (i.e., decrease, increase, and no change). These different responses corresponded with three similar types of response in mean arterial pressure. In spinalized animals, the stimuli produced only increases in both catecholamine secretion and nerve activity, and abdominal stimulation elicited a larger response than hindlimb stimulation. The responses of adrenal nerve activity were eliminated after surgically severing the afferent nerves innervating the abdomen and hindlimb. These findings indicate that the secretion of adrenal medullary hormones is controlled reflexively by acupuncture-like stimulation via excitation of somatic afferent nerves and also via the reflex responses of adrenal sympathetic efferent nerves. Both the spinal cord and supraspinal structures act as reflex centers. The excitatory reflex properties at the propriospinal and segmental levels are modified into a generalized, either excitatory or inhibitory, response by supraspinal structures.
Asunto(s)
Terapia por Acupuntura , Médula Suprarrenal/fisiología , Epinefrina/metabolismo , Norepinefrina/metabolismo , Sistema Nervioso Simpático/fisiología , Abdomen , Anestesia , Animales , Miembro Posterior , Masculino , Ratas , Ratas Wistar , Reflejo/fisiologíaAsunto(s)
Glándulas Suprarrenales/efectos de los fármacos , Gónadas/efectos de los fármacos , Hipotálamo/efectos de los fármacos , Fenetilaminas/farmacología , Hipófisis/efectos de los fármacos , Plantas/química , Rumiantes/fisiología , Glándulas Suprarrenales/fisiología , Médula Suprarrenal/efectos de los fármacos , Médula Suprarrenal/fisiología , Animales , Gónadas/fisiología , Hipotálamo/fisiología , Fenetilaminas/toxicidad , Hipófisis/fisiologíaAsunto(s)
Médula Suprarrenal/fisiología , Hipotálamo/fisiología , Glándula Pineal/fisiología , Reserpina/farmacología , Sistema Nervioso Simpático/fisiología , Médula Suprarrenal/metabolismo , Animales , Depresión/inducido químicamente , Depresión/fisiopatología , Dopamina/metabolismo , Hipotálamo/metabolismo , Masculino , Norepinefrina/metabolismo , RatasRESUMEN
The effects of the protein synthesis inhibitors actinomycin D and cycloheximide on the cellular content of the calcium binding protein synexin, and on the secretory response of cultured bovine adrenal medullary chromaffin cells were determined. Both protein synthesis inhibitors produced a slow decrease in the cellular synexin content. The synexin level was reduced by 50% after 133 h of incubation in the presence of 2 micrograms/ml actinomycin D or 5 micrograms/ml cycloheximide. However, this was partly due to an artefactual stabilization of synexin, since metabolic labelling of synexin with [35S]methionine showed that the half-time of degradation was only 40 h. The secretory response of chromaffin cells was quickly diminished in the presence of protein synthesis inhibitors. Catecholamine secretion induced by membrane depolarization or barium stimulation of intact cells, or by calcium stimulation of digitonin-permeabilized cells was decreased by 77-82% after 24 h of incubation in the presence of 5 micrograms/ml cycloheximide. These results suggest that, in addition to synexin, at least one or more proteins with a shorter half-time of degradation than synexin are involved in the secretory response of adrenal chromaffin cells.
Asunto(s)
Médula Suprarrenal/fisiología , Anexina A7/metabolismo , Catecolaminas/metabolismo , Cicloheximida/farmacología , Dactinomicina/farmacología , Oligonucleótidos Antisentido/farmacología , Médula Suprarrenal/citología , Médula Suprarrenal/efectos de los fármacos , Análisis de Varianza , Animales , Anexina A7/biosíntesis , Compuestos de Bario/farmacología , Secuencia de Bases , Cloruro de Calcio/farmacología , Bovinos , Línea Celular , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Cloruros/farmacología , Hipotálamo , Cinética , Leucina/metabolismo , Potenciales de la Membrana/efectos de los fármacos , Ratones , Datos de Secuencia Molecular , Neuronas , Células PC12 , Cloruro de Potasio/farmacología , Ratas , Uridina/metabolismoRESUMEN
A K+ channel was incorporated into voltage-clamped planar lipid bilayers from bovine chromaffin granules and resealed granule membranes ("ghosts"). It was not incorporated from plasma membrane-rich fractions from the adrenal medulla. The channel had a conductance of approximately 400 pS in symmetric 450 mM KCl, with the permeability sequence K+ > Rb+ > Cs+ > Na+ > Li+, and was insensitive to both Ca2+ and charybdotoxin. It exhibited complex gating kinetics, consistent with the presence of multiple open and closed states, and its gating was voltage-dependent. The channels appeared to incorporate into bilayers with the same orientation, and were blocked from one side (the side of vesicle addition) by 0.2-1 mM TEA+. The block was slightly voltage-dependent. Acidification of resealed granule membranes in response to external ATP (which activated the vacuolar-type ATPase) was significantly reduced in the presence of 1 mM intralumenal TEACl (with 9 mM KCl), and parallel measurements with the potential-sensitive dye Oxonol V showed that such vesicles tended to develop higher internal-positive membrane potentials than control vesicles containing only 10 mM KCl. 1 mM TEA+ had no effect on proton-pumping activity when applied externally, and did not directly affect either the proton-pumping or ATP hydrolytic activity of the partially-purified ATPase. These results suggest that chromaffin granule membranes contain a TEA(+)-sensitive K+ channel which may have a role in regulating the vesicle membrane potential.
Asunto(s)
Gránulos Cromafines/fisiología , Membranas Intracelulares/fisiología , Canales de Potasio/fisiología , Médula Suprarrenal/fisiología , Animales , Calcio/farmacología , Cationes Monovalentes/metabolismo , Bovinos , Caribdotoxina , Membranas Intracelulares/efectos de los fármacos , Cinética , Membrana Dobles de Lípidos , Potenciales de la Membrana/efectos de los fármacos , Canales de Potasio/análisis , Canales de Potasio/efectos de los fármacos , ATPasas de Translocación de Protón/metabolismo , Venenos de Escorpión/farmacologíaRESUMEN
The effects of acute treatment (i.p.) with selenium (Se) on glucoregulation, by measuring plasma levels of adrenocorticotropic hormone (ACTH), beta-endorphin (beta-EN), corticosterone (CORT) and glucose over time, were investigated. The hormones of the hypothalamic-pituitary adrenal (HPA) axis, were measured after treating rats with saline, Se: 1.6 mg/kg, or 3.8 mg/kg. Blood samples were collected before, 30, 60 and 90 min following injection. The results show that i.p. administration of Se (both doses) induce a rise in plasma ACTH, and beta-EN (P < 0.01). Plasma CORT and glucose levels also rose sharply by 30 min (P < 0.05). Corticosterone levels were increased in a dose-dependent fashion over the ensuing hour. Bilateral adrenal demedullation resulted in the abolishment of the Se-induced rise in plasma glucose. Pretreatment with metyrapone (300 mg/kg) was found to delay the Se-induced rise in plasma glucose. The results indicate that after a Se challenge the HPA axis is activated. In addition, CORT was found to be essential in the Se-induced rise in plasma glucose.
Asunto(s)
Hormona Adrenocorticotrópica/sangre , Glucemia/análisis , Corticosterona/sangre , Metirapona/farmacología , Selenio/farmacología , betaendorfina/sangre , Médula Suprarrenal/fisiología , Animales , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
We previously reported that intraventricular prostaglandins (PGs) produced hyperthermia and hyperglycemia in anesthetized rats. However, the relationship of them is little known. We examined the relationship between hyperthermia and hyperglycemia induced by intraventricular PGF2 alpha using curarized and adrenal demedullated rats. Iv curare completely prevented the PGF2 alpha-induced hyperthermia, but enhanced the hyperglycemic effect of PGF2 alpha. Adrenal demedullation completely prevented the hyperglycemia, but did not affect the hyperthermic effect of PGF2 alpha. To further assess the site of action concerned with PGF2 alpha-induced thermoregulation and glucoregulation in the central nervous system (CNS), we injected saline or PGF2 alpha into the preoptic area of the anterior hypothalamus (POA) in intact rats. After microinjection of PGF2 alpha into the POA, the rectal temperature rose, but the plasma glucose level did not increase significantly, as compared with saline-treated control rats. These results suggest that PGF2 alpha causes the central nervous system to produce hyperthermia via shivering, stimulated the somatic motor system, and to produce hyperglycemia by stimulating central sympathetic outflow to the adrenal medulla, but these operate independently under different neural regulation, and these sensitive sites are organically dissociated in the CNS.