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1.
Parkinsonism Relat Disord ; 20(6): 647-50, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24679736

RESUMO

BACKGROUND: Entrainment, the change or elimination of tremor as patients perform a voluntary rhythmical movement by the unaffected limb, is a key diagnostic hallmark of psychogenic tremor. OBJECTIVE: To evaluate the feasibility of using entrainment as a bedside therapeutic strategy ('retrainment') in patients with psychogenic tremor. METHODS: Ten patients with psychogenic tremor (5 women, mean age, 53.6 ± 12.8 years; mean disease duration 4.3 ± 2.7 years) were asked to participate in a pilot proof-of-concept study aimed at "retraining" their tremor frequency. Retrainment was facilitated by tactile and auditory external cueing and real-time visual feedback on a computer screen. The primary outcome measure was the Tremor subscale of the Rating Scale for Psychogenic Movement Disorders. RESULTS: Tremor improved from 22.2 ± 13.39 to 4.3 ± 5.51 (p = 0.0019) at the end of retrainment. The benefits were maintained for at least 1 week and up to 6 months in 6 patients, with relapses occurring in 4 patients between 2 weeks and 6 months. Three subjects achieved tremor freedom. CONCLUSIONS: Tremor retrainment may be an effective short-term treatment strategy in psychogenic tremor. Although blinded evaluations are not feasible, future studies should examine the long-term benefits of tremor retrainment as adjunctive to psychotherapy or specialized physical therapy.


Assuntos
Biorretroalimentação Psicológica/métodos , Transtornos Psicofisiológicos/fisiopatologia , Tremor/psicologia , Tremor/reabilitação , Adulto , Idoso , Sinais (Psicologia) , Estimulação Elétrica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Movimento , Resultado do Tratamento
2.
Br J Pharmacol ; 153(5): 947-55, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18084312

RESUMO

BACKGROUND AND PURPOSE: Inhibition of bradykinin metabolizing enzymes (BMEs) can cause acute angioedema, as demonstrated in a recent clinical trial in patients administered the antihypertensive, omapatrilat. However, the relative contribution of specific BMEs to this effect is unclear and confounded by the lack of a predictive pre-clinical model of angioedema. EXPERIMENTAL APPROACH: Rats were instrumented to record blood pressure and heart rate; inhibitors were infused for 35 min and bradykinin was infused during the last 5 min to elicit hypotension, as a functional marker of circulating bradykinin and relative angioedema risk. KEY RESULTS: In the presence of omapatrilat bradykinin produced dose-dependent hypotension, an effect abolished by B(2) blockade. In the presence of lisinopril (ACE inhibitor), but not candoxatril (NEP inhibitor) or apstatin (APP inhibitor), bradykinin also elicited hypotension. Lisinopril-mediated hypotension was unchanged with concomitant blockade of NEP or NEP/DPPIV (candoxatril+A-899301). However, hypotension was enhanced upon concomitant blockade of APP and further intensified in the presence of NEP inhibition to values not different from omapatrilat alone. CONCLUSIONS AND IMPLICATIONS: We demonstrated that bradykinin is degraded in vivo with an enzyme rank-efficacy of ACE>APP>>NEP or DPPIV. These results suggest the effects of omapatrilat are mediated by inhibition of three BMEs, ACE/APP/NEP. However, dual inhibition of ACE/NEP or ACE/NEP/DPPIV elicits no increased risk of angioedema compared to ACE inhibition alone. Thus, novel BME inhibitors must display no activity against APP to avoid angioedema risk due to high prevalence of ACE inhibitor therapy in patients with diabetes and cardiovascular disease.


Assuntos
Angioedema/etiologia , Bradicinina/metabolismo , Inibidores Enzimáticos/farmacologia , Hipotensão/etiologia , Aminopeptidases/antagonistas & inibidores , Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Animais , Bradicinina/efeitos dos fármacos , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos/métodos , Indanos/farmacologia , Lisinopril/farmacologia , Masculino , Neprilisina/antagonistas & inibidores , Peptídeos/farmacologia , Propionatos/farmacologia , Piridinas/administração & dosagem , Piridinas/farmacologia , Ratos , Ratos Sprague-Dawley , Tiazepinas/administração & dosagem , Tiazepinas/farmacologia
3.
FASEB J ; 15(3): 700-6, 2001 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-11259388

RESUMO

Oxidative stress has been implicated as a causal factor in the aging process of the heart and other tissues. To determine the extent of age-related myocardial oxidative stress, oxidant production, antioxidant status, and oxidative DNA damage were measured in hearts of young (2 months) and old (28 months) male Fischer 344 rats. Cardiac myocytes isolated from old rats showed a nearly threefold increase in the rate of oxidant production compared to young rats, as measured by the rates of 2,7-dichlorofluorescin diacetate oxidation. Determination of myocardial antioxidant status revealed a significant twofold decline in the levels of ascorbic acid (P = 0.03), but not alpha-tocopherol. A significant age-related increase (P = 0.05) in steady-state levels of oxidative DNA damage was observed, as monitored by 8-oxo-2'-deoxyguanosine levels. To investigate whether dietary supplementation with (R)-alpha-lipoic acid (LA) was effective at reducing oxidative stress, young and old rats were fed an AIN-93M diet with or without 0.2% (w/w) LA for 2 wk before death. Cardiac myocytes from old, LA-supplemented rats exhibited a markedly lower rate of oxidant production that was no longer significantly different from that in cells from unsupplemented, young rats. Lipoic acid supplementation also restored myocardial ascorbic acid levels and reduced oxidative DNA damage. Our data indicate that the aging rat heart is under increased mitochondrial-induced oxidative stress, which is significantly attenuated by lipoic acid supplementation.


Assuntos
Envelhecimento/fisiologia , Antioxidantes/farmacologia , Miocárdio/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ácido Tióctico/farmacologia , Animais , Antioxidantes/administração & dosagem , Ácido Ascórbico/farmacologia , Células Cultivadas , Dano ao DNA , Suplementos Nutricionais , Corantes Fluorescentes/metabolismo , Coração/efeitos dos fármacos , Coração/fisiologia , Masculino , Miocárdio/citologia , Oxidantes/biossíntese , Oxidantes/metabolismo , Consumo de Oxigênio , Ratos , Ratos Endogâmicos F344 , Ácido Tióctico/administração & dosagem , Vitamina E/farmacologia
5.
Thromb Haemost ; 81(2): 301-5, 1999 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-10064010

RESUMO

Catheter-directed thrombolysis has gained increasing acceptance for the treatment of patients who present with vascular occlusion; however, intravenous injection may be preferable in selected patients. Recombinant prourokinase (r-proUK) is a recently-developed fibrin-selective thrombolytic agent with specificity for clot-bound plasminogen. To compare the effects of r-proUK on clot lysis and restoration of blood flow when injected by either intraarterial or intravenous routes of administration, we utilized a dog model of arterial thrombosis in which a radiolabelled clot is formed in the femoral artery. The r-proUK was given by intravenous infusion to one group of 18 animals in doses ranging from 10,000 IU/kg to 100,000 IU/kg; a second group of 27 dogs was treated with r-proUK administered by the intra-arterial route in a dose range from 300 IU to 10,000 IU. Clot lysis was measured by monitoring the loss of counts from the radiolabelled clot over time; blood flow was also monitored throughout the experimental period. Animals which received intravenous treatment showed dose-related clot lysis ranging from 14% to 70% at 2 h, while those which received intra-arterial infusions showed lysis ranging from 22% to 79% over the same period. For similar degrees of clot lysis attained at the highest dose levels of 100,000 IU/kg and 10,000 IU, blood flow was restored to 77% and 35% of control levels in dogs which received intravenous and intraarterial treatment, respectively. The hemostatic protein fibrinogen was not reduced in any of the treatment groups. The results indicate that 100 times more intravenous than intra-arterial r-proUK is required to produce similar clot lysis in this canine model, and that the agent can be administered at this level without induction of a systemic lytic state.


Assuntos
Arteriopatias Oclusivas/tratamento farmacológico , Artéria Femoral , Fibrinolíticos/uso terapêutico , Terapia Trombolítica , Trombose/tratamento farmacológico , Ativador de Plasminogênio Tipo Uroquinase/uso terapêutico , Animais , Cães , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos , Fibrinolíticos/administração & dosagem , Membro Posterior/irrigação sanguínea , Infusões Intra-Arteriais , Infusões Intravenosas , Injeções Intravenosas , Masculino , Proteínas Recombinantes de Fusão/administração & dosagem , Proteínas Recombinantes de Fusão/uso terapêutico , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/genética , Proteínas Recombinantes/uso terapêutico , Fluxo Sanguíneo Regional/efeitos dos fármacos , Ativador de Plasminogênio Tipo Uroquinase/administração & dosagem , Ativador de Plasminogênio Tipo Uroquinase/genética
6.
Behav Res Ther ; 35(9): 859-62, 1997 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-9299806

RESUMO

Sixty-four men and 49 women who applied for admission to outpatient substance abuse programs provided information on their preferred chemical (e.g., alcohol) and information on their alcohol and other chemical use. They also completed a package of self-report questionnaires including the Anxiety Sensitivity Index (ASI). The results showed that men who scored high on the ASI were more likely than low ASI subjects to prefer depressants, especially alcohol. Subjects who scored low on the ASI were more likely to prefer marijuana. ASI score did not predict chemical preference among women. All female ASI groups (high, medium and low) showed a preference for alcohol. The implications of these findings are discussed.


Assuntos
Ansiedade/complicações , Comportamento de Escolha , Transtornos Relacionados ao Uso de Substâncias/psicologia , Adulto , Consumo de Bebidas Alcoólicas/psicologia , Análise de Variância , Depressores do Sistema Nervoso Central , Estimulantes do Sistema Nervoso Central , Distribuição de Qui-Quadrado , Estudos Transversais , Feminino , Humanos , Masculino , Fumar Maconha/psicologia , Fatores Sexuais
8.
J Genet Psychol ; 157(4): 425-41, 1996 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-8955425

RESUMO

Preschool children's resistance to the influence of postevent misinformation was investigated. Ninety-one preschoolers (3 years 6 months to 5 years 6 months old) were read a story about a boy's birthday party. One week later, they received 1 of 3 summary conditions containing general information (unbiased, biased, or no summary). Two weeks after the original story, they were presented with either a biased summary or no summary. The children's suggestibility was assessed by a recognition test that provided a choice between the original and postevent misinformation. Those who received an unbiased summary showed higher recognition rates than those who received a biased summary, regardless of whether the biased information had been given at the 1- or 2-week interval. Although an unbiased summary followed by biased information did not produce greater recognition rates that were found in the control group, participants who received unbiased summaries did perform above chance, suggesting that even a vague summary may help to reactivate specific memory traces, particularly when information is bimodally presented.


Assuntos
Percepção da Fala , Sugestão , Atenção , Pré-Escolar , Feminino , Humanos , Masculino , Memória
9.
Brain Res Mol Brain Res ; 40(1): 153-6, 1996 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-8840025

RESUMO

We investigated the effects of sustained administration of cocaine on the regulation of prodynorphin gene expression in rat brain. Intracerebroventricular (i.c.v.) infusion of cocaine hydrochloride (30 micrograms/day) for 7 days, by means of osmotic minipumps, elicited a significant 35% decrease of prodynorphin mRNA levels in rat hypothalamus and increase (22%) in caudate-putamen. At the same time and in the same animals, no significant changes were detected in the hippocampus or in the nucleus accumbens. These results indicate that continuously infused cocaine is able to modulate expression of the prodynorphin gene in opposite directions or has no effect on prodynorphin expression, depending on the brain region analysed. Cocaine, as well as opiates, might activate specific neuronal pathways, shared by different classes of drugs of abuse, involving, at least in part, the endogenous opioid system.


Assuntos
Núcleo Caudado/metabolismo , Ventrículos Cerebrais/fisiologia , Cocaína/farmacologia , Encefalinas/biossíntese , Hipotálamo/metabolismo , Precursores de Proteínas/biossíntese , Putamen/metabolismo , Transcrição Gênica/efeitos dos fármacos , Animais , Núcleo Caudado/efeitos dos fármacos , Ventrículos Cerebrais/efeitos dos fármacos , Cocaína/administração & dosagem , Hipotálamo/efeitos dos fármacos , Infusões Parenterais , Masculino , Putamen/efeitos dos fármacos , RNA Mensageiro/análise , RNA Mensageiro/biossíntese , Ratos , Ratos Endogâmicos F344
10.
Br J Pharmacol ; 117(1): 161-9, 1996 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-8825358

RESUMO

1. Morphine produces a plethora of pharmacological effects and its chronic administration induces several side-effects. The cellular mechanisms by which opiates induce these side-effects are not fully understood. Several studies suggest that regulation of adenylyl cyclase activity by opioids and other transmitters plays an important role in the control of neural function. 2. The aim of this study was to evaluate desensitization of mu- and delta- opioid receptors, defined as a reduced ability of opioid agonists to inhibit adenylyl cyclase activity, in four different brain structures known to be involved in opiate drug actions: caudate putamen, nucleus accumbens, thalamus and periaqueductal gray (PAG). Opiate regulation of adenylyl cyclase in these regions has been studied in control and morphine-dependent rats. 3. The chronic morphine treatment used in the present study (subcutaneous administration of 15.4 mg morphine/rat/day for 6 days via osmotic pump) induced significant physical dependence as indicated by naloxone-precipitated withdrawal symptoms. 4. Basal adenylyl cyclase in the four brain regions was not modified by this chronic morphine treatment. In the PAG and the thalamus, a desensitization of mu- and delta-opioid receptors was observed, characterized by a reduced ability of Tyr-D-Ala-Gly-(NMe)Phe-Gly-ol (DAMGO; mu), Tyr-D-Pen-Gly-Phe-D-Pen (DPDPE; delta) and [D-Ala2]-deltorphin-II (DT-II; delta) to inhibit adenylyl cyclase, activity following chronic morphine treatment. 5. The opioid receptor desensitization in PAG and thalamus appeared to be heterologous since the metabotropic glutamate receptor agonists, L-AP4 and glutamate, and the 5-hydroxytryptamine (5-HT)1A receptor agonist, R(+)-8-hydroxy-2-(di-n-propylamino)tetralin hydrobromide (8-OH-DPAT), also showed reduced inhibition of adenylyl cyclase activity following chronic morphine treatment. 6. In the nucleus accumbens and the caudate putamen, desensitization of delta-opioid receptor-mediated inhibition without modification of mu-opioid receptor-mediated inhibition was observed. An indirect mechanism probably involving dopaminergic systems is proposed to explain the desensitization of delta-mediated responses and the lack of mu-opioid receptor desensitization after chronic morphine treatment in caudate putamen and nucleus accumbens. 7. These results suggest that adaptive responses occurring during chronic morphine administration are not identical in all opiate-sensitive neural populations.


Assuntos
Adenilil Ciclases/metabolismo , Encéfalo/efeitos dos fármacos , Dependência de Morfina/fisiopatologia , Morfina/farmacologia , Receptores Opioides delta/efeitos dos fármacos , Receptores Opioides mu/efeitos dos fármacos , 8-Hidroxi-2-(di-n-propilamino)tetralina/farmacologia , Aminobutiratos/farmacologia , Analgésicos/farmacologia , Animais , Encéfalo/fisiopatologia , Núcleo Caudado/efeitos dos fármacos , Núcleo Caudado/fisiopatologia , Ala(2)-MePhe(4)-Gly(5)-Encefalina , D-Penicilina (2,5)-Encefalina , Encefalinas/farmacologia , Ácido Glutâmico/farmacologia , Masculino , Naloxona , Antagonistas de Entorpecentes , Núcleo Accumbens/efeitos dos fármacos , Núcleo Accumbens/fisiopatologia , Oligopeptídeos/farmacologia , Substância Cinzenta Periaquedutal/efeitos dos fármacos , Substância Cinzenta Periaquedutal/fisiopatologia , Ratos , Ratos Sprague-Dawley , Agonistas do Receptor de Serotonina/farmacologia , Síndrome de Abstinência a Substâncias , Tálamo/efeitos dos fármacos , Tálamo/fisiopatologia
11.
Mol Pharmacol ; 48(2): 189-93, 1995 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-7651350

RESUMO

In ND8-47 cells, a neuroblastoma x dorsal root ganglion hybrid cell line, activation of delta-opioid receptors induced an increase in the intracellular free calcium concentration ([Ca2+]i) through dihydropyridine-sensitive calcium channels. This effect was mediated by pertussis toxin-sensitive G proteins. The G protein alpha subunits alpha i2, alpha i3, alpha q, and alpha s were detected using Western blots, whereas alpha o and alpha i1 were not found in ND8-47 cell membranes. To identify the specific G protein alpha subunit(s) responsible for the increase in [Ca2+]i, we treated ND8-47 cells with antisense oligodeoxynucleotides (AS) complementary to the mRNA for each G protein alpha subunit (alpha i2, alpha i3, or alpha s), at a concentration of 10 microM, for up to 6 days and examined their effects on opioid-induced increases in [Ca2+]i and on the levels of G protein alpha subunits. [Ca2+]i was measured in adherent cells using the fluorescent dye fura-2. Treatment of cells with alpha i2-AS (10 microM, for 6 days) resulted in a 73% inhibition of the [D-Ser2,Leu5]-enkephalin-Thr-induced increase in [Ca2+]i. In contrast, pretreatment of cells with alpha i3-AS (10 microM, for 6 days) or alpha s-AS (10 microM, for 6 days) had no effect on the [D-Ser2,Leu5]-enkephalin-Thr-induced responses. Western blots indicated that the levels of alpha i2 were decreased when cells were exposed to alpha i2-AS (10 microM) for 6 days, whereas the levels of alpha i3, alpha s, and alpha q were not affected by this treatment. Treatment of the cells with alpha i3-AS or alpha s-AS for 6 days significantly reduced alpha i3 or alpha s levels, respectively. These results indicate that the opioid-induced increase in [Ca2+]i in ND8-47 cells is mediated by G alpha i2.


Assuntos
Cálcio/metabolismo , Encefalina Leucina/análogos & derivados , Proteínas de Ligação ao GTP/genética , Gânglios Espinais/efeitos dos fármacos , Oligonucleotídeos Antissenso/farmacologia , Analgésicos/antagonistas & inibidores , Sequência de Bases , Canais de Cálcio/efeitos dos fármacos , Células Cultivadas , Encefalina Leucina/antagonistas & inibidores , Gânglios Espinais/citologia , Células Híbridas , Dados de Sequência Molecular , Neuroblastoma/patologia , Receptores Opioides delta/efeitos dos fármacos
12.
J Hypertens ; 9(10): 909-17, 1991 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-1658133

RESUMO

We showed earlier that the rostral ventral medulla can be functionally and anatomically divided into the rostral ventrolateral medulla (RVLM) and the rostral ventromedial medulla (RVMM). In this study, we examined the relationship between the lateral hypothalamus and these two medullary sites. Electrical stimulation of the lateral hypothalamus produced a pressor response mediated by increases in renal and mesenteric vascular resistance. Inactivating RVLM had no effect on this response whereas inactivating RVMM significantly blunted the pressor response and the increases in renal and mesenteric resistance. In other studies, inactivating dorsomedullary sites significantly reduced arterial pressure. Unlike RVLM, these depressor responses were not significantly altered by reducing tidal volume. Inactivating sites 0.5 mm medial and lateral to the RVMM, as well as a site 0.5 mm caudal to the RVLM, resulted in depressor responses that were unaffected by reducing tidal volume. However, inactivation of a site 1.0 mm caudal to the RVLM but still within the ventrolateral medullary pressor area, resulted in a depressor response that was enhanced by reduced tidal volume. Together, these data demonstrate a functional differentiation of medullary sites controlling vasomotor outflow.


Assuntos
Pressão Sanguínea/fisiologia , Bulbo/fisiologia , Tálamo/fisiologia , Animais , Pressão Sanguínea/efeitos dos fármacos , Estimulação Elétrica , Injeções , Rim/irrigação sanguínea , Lidocaína/administração & dosagem , Bulbo/efeitos dos fármacos , Artérias Mesentéricas/efeitos dos fármacos , Artérias Mesentéricas/fisiologia , Veias Mesentéricas/efeitos dos fármacos , Veias Mesentéricas/fisiologia , Ratos , Ratos Endogâmicos , Resistência Vascular/efeitos dos fármacos , Resistência Vascular/fisiologia
13.
Neuropharmacology ; 26(7B): 987-96, 1987 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-2821438

RESUMO

The ability of opioids to inhibit the release of norepinephrine (NE) from slice preparations of brain has been tested. Slices of brain were preincubated with [3H]NE allowing uptake of the [3H]NE into intraneuronal stores of NE. After rinsing, the tissues were incubated at 37 degrees C in Krebs buffer containing 5mM K+, for estimation of baseline release and then in 20 mM K+ to stimulate release. The [3H]NE released into the incubation medium was increased by blockade of neuronal re-uptake with desipramine and by blockade of alpha 2-adrenoceptors with yohimbine. These agents were used routinely in subsequent incubations. Release was also Ca2+ dependent. Stimulated release of [3H]NE from slices of cortex of the guinea pig and rat was inhibited by the mu opioid receptor agonist, Tyr-D-Ala2-Gly-NMePhe-Gly-ol (DAGO) in a naloxone-reversible manner, although naloxone itself produced a measurable inhibitory effect in the absence of opioid agonist. Stimulated release of [3H]NE from slices of guinea pig cortex was also inhibited by the delta receptor selective peptide, [D-Pen2, D-Pen5] enkephalin (DPDPE), and the kappa receptor selective agent, U50,488H. The inhibitory effect of both agents was reversed by naloxone. In rat cortex, DAGO induced a similar inhibition of release to that seen in guinea pig cortex, but DPDPE and U50,488H were much less effective, producing only weak inhibition even in large doses. Similar results were obtained when effects of opioids on [3H]NE release from hippocampus and cerebellum of the guinea pig and rat were compared. In guinea pig tissues, agonists acting preferentially through mu, delta and kappa receptors were all active in inhibiting stimulated release of [3H]NE, but in hippocampus and cerebellum of the rat, only DAGO inhibited release while DPDPE and U50,488H either had no effect or potentiated the stimulated release. These results suggest that in the rat only mu type opioid receptors mediate an inhibitory regulation of NE release from the cortex, hippocampus and cerebellum terminal projections of locus coeruleus noradrenergic neurons. In the guinea pig, stimulated release of [3H]NE was subject to inhibitory regulation by mu, delta and kappa opioid receptors.


Assuntos
Encéfalo/metabolismo , Norepinefrina/metabolismo , Receptores Opioides/fisiologia , (trans)-Isômero de 3,4-dicloro-N-metil-N-(2-(1-pirrolidinil)-ciclo-hexil)-benzenoacetamida , Animais , Cálcio/metabolismo , Ala(2)-MePhe(4)-Gly(5)-Encefalina , D-Penicilina (2,5)-Encefalina , Encefalinas/metabolismo , Encefalinas/farmacologia , Modelos Neurológicos , Naloxona/farmacologia , Potássio/metabolismo , Pirrolidinas/farmacologia
14.
N Z Vet J ; 35(4): 55-7, 1987 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-16031373

RESUMO

Ewes rearing twin lambs on a restricted ration of irrigated pasture were either supplemented daily with 12.5 mg magnesium chloride or not. Serum magnesium levels measured 24 hours after the previous day's dose did not differ between treatments. They averaged 0.74 mmol/l during the period of supplementation with 36% of values below 0.7 mmol/l, the lower limit of the "normal" range. Milk consumption by and liveweight gains of lambs were not increased by magnesium supplementation indicating that ewe magnesium levels below 0.7 mmol/l serum did not limit production in this instance.

15.
J Neurochem ; 43(6): 1616-23, 1984 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-6149267

RESUMO

Homogenates of rat anterior lobe (AL) and neurointermediate lobe (NIL) pituitary and rat hypothalamus were subjected to subcellular fractionation and density gradient centrifugation. The subcellular distribution of immunoreactive dynorophin A (ir-Dyn A) in NIL was found to be similar to that of ir-arginine vasopressin (ir-AVP). ir-Dyn A migrated as a discrete band on sucrose density gradients, which corresponded in sedimentation rate to that of ir-AVP, suggesting that these two peptides are stored within organelles of similar size and density. Two other products of prodynorphin, ir-alpha-neoendorphin (ir-alpha-nEND) and ir-Dyn A-(1-8) also comigrated with ir-AVP. ir-[Leu5]-enkephalin (ir-LE), which may be a product of prodynorphin or proenkephalin, was also found to migrate in this region of the gradient. When a homogenate of rat hypothalamus was prepared using a method that has been developed for synaptosome isolation, ir-Dyn A was found to comigrate with Na+/K+-activated adenosine triphosphatase (Na/K-ATPase), a synaptosomal marker enzyme. Using a more concentrated homogenate ir-Dyn A was found to migrate to a less dense region where peptide-containing synaptic vesicles have previously been localized. When a synaptosomal preparation was lysed in hypotonic solution a shift was seen in the migration rate of ir-Dyn A to this region of the gradient (containing putative synaptic vesicles). Thus the bulk of hypothalamic dynorphin appears to be present within synaptosome-like structures which, upon lysis, release a less dense, smaller subcellular organelle corresponding in sedimentation characteristics to other types of peptide-containing synaptic vesicles.(ABSTRACT TRUNCATED AT 250 WORDS)


Assuntos
Endorfinas/metabolismo , Hipotálamo/ultraestrutura , Hipófise/ultraestrutura , Animais , Arginina Vasopressina/metabolismo , Centrifugação com Gradiente de Concentração , Dinorfinas/metabolismo , Encefalina Leucina/metabolismo , Encefalina Metionina/análogos & derivados , Encefalina Metionina/metabolismo , Masculino , Fragmentos de Peptídeos/metabolismo , Precursores de Proteínas/metabolismo , Ratos , Ratos Endogâmicos , Frações Subcelulares/metabolismo , Vesículas Sinápticas/metabolismo , Sinaptossomos/metabolismo
16.
Neurosci Lett ; 33(2): 179-84, 1982 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-6130498

RESUMO

The distribution of the opioid peptide, dynorphin, has been studied in discrete, microdissected hypothalamic nuclei, and compared with the distribution of vasopressin. Both peptides were found in relatively high concentration in the supraoptic and paraventricular nuclei. However, dynorphin-like immunoreactivity (DYN-LI) was much more widely distributed in the hypothalamus than vasopressin-like immunoreactivity, with highest concentrations in the anterior hypothalamic and ventromedial nuclei. DYN-LI was also observed in some extra-hypothalamic structures; concentrations which were comparable to the highest levels in the hypothalamus were found in the tractus diagonalis and the nucleus interstitialis stria terminalis. Among the three brainstem nuclei examined, DYN-LI levels were highest in the sensory nucleus of the trigeminal nerve.


Assuntos
Endorfinas/metabolismo , Hipotálamo/metabolismo , Vasopressinas/metabolismo , Animais , Diencéfalo/metabolismo , Dinorfinas , Masculino , Núcleo Hipotalâmico Paraventricular/metabolismo , Ratos , Ratos Endogâmicos , Núcleo Supraquiasmático/metabolismo , Núcleo Supraóptico/metabolismo , Telencéfalo/metabolismo , Núcleo Hipotalâmico Ventromedial/metabolismo
17.
Life Sci ; 31(16-17): 1765-8, 1982.
Artigo em Inglês | MEDLINE | ID: mdl-6130435

RESUMO

Dynorphin is found mainly in the particulate fraction of rat pituitary gland and hypothalamus homogenates. Dynorphin-like immunoreactivity (DYN-LI) from neurointermediate lobe (NIL) homogenates migrates at the same rate as vasopressin-like immunoreactivity (AVP-LI), in sucrose density gradients, whereas DYN-LI from the hypothalamus appears to migrate principally in a less dense region of the gradient. This suggests that dynorphin and vasopressin from pituitary are present in organelles of similar size and density, while the bulk of the dynorphin in the hypothalamus appears to be stored in a different subcellular organelle. Anterior lobe (AL) dynorphin appears to migrate in two separate bands on density gradients: the less dense band (slower) migrates at a similar rate to that of dynorphin and vasopressin from NIL. When alpha-neo-endorphin was measured in sucrose gradients of NIL and hypothalamus, it was found to co-migrate with DYN-LI.


Assuntos
Endorfinas/análise , Hipotálamo/análise , Hipófise/análise , Vasopressinas/análise , Animais , Dinorfinas , Hipotálamo/ultraestrutura , Masculino , Hipófise/ultraestrutura , Radioimunoensaio , Ratos , Ratos Endogâmicos , Distribuição Tecidual
18.
J Pharm Pharmacol ; 34(7): 438-41, 1982 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-6126540

RESUMO

5-hydroxytryptamine (5-HT) (3 X 10(-9) to 10(-6) M) produced a concentration-related inhibition of potassium-evoked tritium release from slices of rat hypothalamus preloaded with [3H]-5-HT. The response to 5-HT was unaffected by the presence of yohimbine (10(-6) M), pimozide (10(-7) M), domperidone (10(-7) M) or tetrodotoxin (10(-7) M), indicating that the response was not mediated via alpha 1- or alpha 2-adrenoceptors or dopamine receptors and that the receptors that were involved were located directly on the 5-HT nerve terminal. The 5-HT antagonist metergoline (10(-8) to 3 X 10(-7) M) produced a parallel rightward shift in the concentration-effect curve to 5-HT with no reduction in the size of the maximum response. The pA10 value for metergoline was 6.82 and the slope of the Arunlakshana-Schild plot was not significantly different from 1.0 indicating that it was a competitive antagonist. Methiothepin produced a similar effect to metergoline whilst cyproheptadine and methysergide were less potent as antagonists of 5-HT and were not competitive. Cinanserin was inactive. Thus we have characterized the 5-HT autoreceptor in the rat hypothalamus using a classical pharmacological approach and found that it has more in common with the autoreceptor which we have previously identified in the raphe nuclei of the rat than it has with the 5-HT receptor located on dopamine neuroterminals in the striatum.


Assuntos
Hipotálamo/metabolismo , Receptores de Serotonina/efeitos dos fármacos , 5-Metoxitriptamina/farmacologia , Animais , Clomipramina/farmacologia , Masculino , Potássio/farmacologia , Ratos , Serotonina/metabolismo
20.
Biochim Biophys Acta ; 688(1): 211-7, 1982 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-6284229

RESUMO

Neuroblastoma x glioma cells NG108-15 were cultured in lipid-free medium supplemented with fatty acids of various chain length and unsaturation. Binding of 3H-labelled [DAla2]-[DLeu5]-enkephalin by membranes of cells grown in saturation fatty acids of different chain length was not significantly different from that of the control On the other hand, a proportional decrease of binding capacity with no change in residual receptor affinity was noticed when cells were cultured in medium containing fatty acids of increasing unsaturation. This decrease was time dependent and reached a maximum at about 48 h. Binding of [3H]dihydromorphine and [3H]naloxone was similarly affected. In contrast, when membranes of cells grown in normal medium were preincubated up to 3 h with unsaturated fatty acid and tested for opioid binding, no significant reduction was observed. Examination of the fatty acid composition of phospholipid from cells grown in linolenate indicated that a significant alteration of the acyl composition has occurred. To evaluate the underlying cause of this type of inhibition, the effect of linolenic acid on cell growth and protein synthesis was examined. When cells were cultured in 100 microM of this fatty acid, both growth and protein synthesis were retarded by 28% and 19%, respectively. Since opiate receptors are proteineous in nature, a reduction of protein synthesis may partially account for the loss of opioid binding activity. On the other hand, an increase of membrane fluidity is known to affect a number of cellular functions, including ligand-receptor recognition. Whether this can offer a satisfactory explanation for our observations remains to be established.


Assuntos
Ácidos Graxos Insaturados/fisiologia , Lipídeos de Membrana/fisiologia , Neurônios/metabolismo , Receptores Opioides/metabolismo , Animais , Linhagem Celular , Di-Hidromorfina/metabolismo , Encefalinas/metabolismo , Cinética , Fluidez de Membrana , Naloxona/metabolismo , Ratos
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