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1.
Am J Physiol Regul Integr Comp Physiol ; 302(7): R815-24, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22262306

RESUMO

Neurons that synthesize melanin-concentrating hormone (MCH) colocalize GABA, regulate energy homeostasis, modulate water intake, and influence anxiety, stress, and social interaction. Similarly, vasopressin and oxytocin can influence the same behaviors and states, suggesting that these neuropeptides may exert part of their effect by modulating MCH neurons. Using whole cell recording in MCH-green fluorescent protein (GFP) transgenic mouse hypothalamic brain slices, we found that both vasopressin and oxytocin evoked a substantial excitatory effect. Both peptides reversibly increased spike frequency and depolarized the membrane potential in a concentration-dependent and tetrodotoxin-resistant manner, indicating a direct effect. Substitution of lithium for extracellular sodium, Na(+)/Ca(2+) exchanger blockers KB-R7943 and SN-6, and intracellular calcium chelator BAPTA, all substantially reduced the vasopressin-mediated depolarization, suggesting activation of the Na(+)/Ca(2+) exchanger. Vasopressin reduced input resistance, and the vasopressin-mediated depolarization was attenuated by SKF-96265, suggesting a second mechanism based on opening nonselective cation channels. Neither vasopressin nor oxytocin showed substantial excitatory actions on lateral hypothalamic inhibitory neurons identified in a glutamate decarboxylase 67 (GAD67)-GFP mouse. The primary vasopressin receptor was vasopressin receptor 1a (V1aR), as suggested by the excitation by V1aR agonist [Arg(8)]vasotocin, the selective V1aR agonist [Phe(2)]OVT and by the presence of V1aR mRNA in MCH cells, but not in other nearby GABA cells, as detected with single-cell RT-PCR. Oxytocin receptor mRNA was also detected in MCH neurons. Together, these data suggest that vasopressin or oxytocin exert a minimal effect on most GABA neurons in the lateral hypothalamus but exert a robust excitatory effect on presumptive GABA cells that contain MCH. Thus, some of the central actions of vasopressin and oxytocin may be mediated through MCH cells.


Assuntos
Arginina Vasopressina/fisiologia , Neurônios GABAérgicos/fisiologia , Hormônios Hipotalâmicos/fisiologia , Hipotálamo/fisiologia , Melaninas/fisiologia , Ocitocina/fisiologia , Hormônios Hipofisários/fisiologia , Animais , Arginina Vasopressina/agonistas , Arginina Vasopressina/farmacologia , Compostos de Benzil/farmacologia , Bloqueadores dos Canais de Cálcio/farmacologia , Canais de Cálcio/efeitos dos fármacos , Quelantes/farmacologia , Ácido Egtázico/análogos & derivados , Ácido Egtázico/farmacologia , Neurônios GABAérgicos/efeitos dos fármacos , Glutamato Descarboxilase/genética , Glutamato Descarboxilase/fisiologia , Hipotálamo/efeitos dos fármacos , Imidazóis/farmacologia , Canais Iônicos/efeitos dos fármacos , Lítio/farmacologia , Potenciais da Membrana/efeitos dos fármacos , Camundongos , Camundongos Transgênicos , Ocitocina/farmacologia , Receptores de Ocitocina/fisiologia , Receptores de Vasopressinas/agonistas , Receptores de Vasopressinas/fisiologia , Trocador de Sódio e Cálcio/antagonistas & inibidores , Trocador de Sódio e Cálcio/fisiologia , Tiazolidinas/farmacologia , Tioureia/análogos & derivados , Tioureia/farmacologia
2.
J Neurosci ; 24(40): 8741-51, 2004 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-15470140

RESUMO

Neurons that release neuropeptide Y (NPY) have important effects on hypothalamic homeostatic regulation, including energy homeostasis, and innervate hypocretin neurons. Using whole-cell patch-clamp recording, we explored NPY actions on hypocretin cells identified by selective green fluorescent protein expression in mouse hypothalamic slices. NPY reduced spike frequency and hyperpolarized the membrane potential of hypocretin neurons. The NPY hyperpolarizing action persisted in tetrodotoxin (TTX), was mimicked by Y1 receptor-selective agonists [Pro34]-NPY and [D-Arg25]-NPY, and was abolished by the Y1-specific antagonist BIBP3226 [(R)-N2-(diphenylacetyl)-N-[(4-hydroxyphenyl)methyl]-D-arginine-amide], consistent with a direct activation of postsynaptic Y1 receptors. NPY induced a current that was dependent on extracellular potassium, reversed near the potassium equilibrium potential, showed inward rectification, was blocked by extracellular barium, and was abolished by GDP-betaS in the recording pipette, consistent with a G-protein-activated inwardly rectifying K+ (GIRK) current. [Pro34]-NPY evoked, and BIBP3226 blocked, the activation of the GIRK-type current, indicating mediation by a Y1 receptor. NPY attenuated voltage-dependent calcium currents mainly via a Y1 receptor subtype. BIBP3226 increased spontaneous spike frequency, suggesting an ongoing Y1 receptor-mediated NPY inhibition. In TTX, miniature EPSCs were reduced in frequency but not amplitude by NPY, NPY13-36, and [D-Trp32]-NPY, but not by [Pro34]-NPY, suggesting the presynaptic inhibition was mediated by a Y2/Y5 receptor. NPY had little effect on GABA-mediated miniature IPSCs but depressed spontaneous IPSCs. Together, these data support the view that NPY reduces the activity of hypocretin neurons by multiple presynaptic and postsynaptic mechanisms and suggest NPY axons innervating hypocretin neurons may tonically attenuate hypocretin-regulated arousal.


Assuntos
Hipotálamo/fisiologia , Peptídeos e Proteínas de Sinalização Intracelular/fisiologia , Neurônios/fisiologia , Neuropeptídeo Y/farmacologia , Neuropeptídeos/fisiologia , Terminações Pré-Sinápticas/fisiologia , Transmissão Sináptica , Potenciais de Ação , Animais , Nível de Alerta , Bário/farmacologia , Canais de Cálcio/metabolismo , Células Cultivadas , Condutividade Elétrica , Canais de Potássio Corretores do Fluxo de Internalização Acoplados a Proteínas G , Proteínas de Fluorescência Verde/análise , Proteínas de Fluorescência Verde/genética , Hipotálamo/citologia , Peptídeos e Proteínas de Sinalização Intracelular/análise , Camundongos , Camundongos Transgênicos , Inibição Neural , Neurônios/efeitos dos fármacos , Neuropeptídeos/análise , Receptores de Orexina , Orexinas , Técnicas de Patch-Clamp , Canais de Potássio Corretores do Fluxo de Internalização/metabolismo , Terminações Pré-Sinápticas/efeitos dos fármacos , Receptores Acoplados a Proteínas G , Receptores de Neuropeptídeos , Receptores de Neuropeptídeo Y/agonistas , Receptores de Neuropeptídeo Y/fisiologia
3.
World J Gastroenterol ; 9(1): 134-6, 2003 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-12508368

RESUMO

AIM: To study the effects of tetrandrine (Tet) on calcium release-activated calcium current (I(CRAC)), delayed rectifier potassium current (I(K)), and inward rectifier potassium currents (I(K1)) in isolated rat hepatocytes. METHODS: Hepatocytes of rat were isolated by using perfusion method. Whole cell patch-clamp techniques were used in our experiment. RESULTS: The peak amplitude of I(CRAC) was -508+/-115 pA (n=15), its reversal potential of I(CRAC) was about 0 mV. At the potential of -100 mV, Tet inhibited the peak amplitude of I(CRAC) from -521+/-95 pA to -338+/-85 pA (P<0.01 vs control, n=5), with the inhibitory rate of 35 % at 10 micromol/L and from -504+/-87 pA to -247+/-82 pA (P<0.01 vs control, n=5), with the inhibitory rate of 49 % at 100 micromol/L, without affecting its reversal potential. The amplitude of I(CRAC) was dependent on extracellular Ca(2+) concentration. The peak amplitude of I(CRAC) was -205+/-105 pA (n=3) in tyrode's solution with Ca(2+) 1.8 mmol/L (P<0.01 vs the peak amplitude of I(CRAC) in external solution with Ca(2+) 10 mmol/L). Tet at the concentration of 10 and 100 micromol/L did not markedly change the peak amplitude of delayed rectifier potassium current and inward rectifier potassium current (P>0.05 vs control). CONCLUSION: Tet protects hepatocytes by inhibiting I(CRAC), which is not related to I(K) and I(K1).


Assuntos
Alcaloides/farmacologia , Benzilisoquinolinas , Bloqueadores dos Canais de Cálcio/farmacologia , Canais de Cálcio/metabolismo , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Canais de Potássio/metabolismo , Animais , Células Cultivadas , Medicamentos de Ervas Chinesas/farmacologia , Feminino , Hepatócitos/citologia , Masculino , Potenciais da Membrana/fisiologia , Técnicas de Patch-Clamp , Ratos , Ratos Wistar
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