Involvement of voltage-operated calcium channels in alpha-melanocyte-stimulating hormone (alpha-MSH) release from perifused rat hypothalamic slices.
The contribution of voltage-operated calcium (VOC) channels in the mechanism of release of alpha-melanocyte-stimulating hormone (alpha-MSH) from hypothalamic neurons was investigated using perifused rat hypothalamic slices. The stimulatory effect of potassium (50 mM) on alpha-MSH release was completely blocked by cadmium (1 mM) a calcium competitor which indifferently blocks T-, L-and N-type VOC channels. To determine the nature of calcium conductances involved in K+-evoked alpha-MSH release, we have investigated the effect of a VOC channel agonist and 3 antagonists on the secretion of the neuropeptide. Administration of synthetic omega-conotoxin fraction GVIA (1 microM), a peptide toxin which blocks both N- and L-type VOC channels, reduced by 33% K+-induced alpha-MSH release. In contrast, the 1,4-dihydropyridine (DHP) antagonist nifedipine, at concentrations up to 100 microM, did not affect the response of hypothalamic alpha-MSH neurons to depolarizing concentrations of KCl. In addition, the secretion of alpha-MSH induced by high K+ concentrations was not reduced by nifedipine (10 microM) in the presence of diltiazem (1 microM), a benzothiazepine derivative which increases the affinity of the DHP antagonist for L-type VOC channels. The DHP agonist BAY K 8644 (0.1-10 microM) did not modify the early phase of the response of alpha-MSH neurons to K+-induced depolarization. In contrast BAY K 8644 (1 or 10 microM) significantly prolonged the duration of K+-induced alpha-MSH release. This sustained release of alpha-MSH induced by BAY K 8644 (10 microM) was totally suppressed by nifedipine (10 microM).(ABSTRACT TRUNCATED AT 250 WORDS)
Tranchand Bunel
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Groupe de Recherche en Endocrinologie Moléculaire, URA CNRS 650, Unité Affiliée à l'INSERM, Université de Rouen, Mont-Saint-Aignan, France.
Blasquez
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Delbende
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Jégou
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Vaudry
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D000818:Animals; D002104:Cadmium / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000502:physiology*; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D000521:alpha-MSH / Q000378:metabolism*
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D002104:Cadmium; D000521:alpha-MSH; D011188:Potassium