Effects of ions and ionic channel activators or blockers on release of alpha-MSH from perifused rat hypothalamic slices.
The involvement of sodium and chloride ions in the process of alpha-melanocyte-stimulating hormone (a-MSH) release from hypothalamic neurons was investigated using perifused rat hypothalamic slices. Three different stimuli were found to increase a-MSH release from hypothalamic slices: high K+ concentration (50 mM), veratridine (50 microM), and the Na+/K(+)-ATPase inhibitor ouabain (1 mM). Spontaneous or K(+)-evoked a-MSH release was insensitive to the specific Na+ channel blocker tetrodotoxin (TTX; 1.5 microM) and to the blocker of K+ channels tetraethylammonium (TEA; 30 mM) or 4-aminopyridine (4-AP; 4 mM). In contrast, blockage of ouabain-sensitive Na+/K(+)-ATPase increased the resting level of a-MSH and caused a dramatic potentiation of K(+)-evoked a-MSH release. The Na+ channel activator veratridine (50 microM) triggered a-MSH release. This stimulatory effect was blocked by TTX and prolonged by TEA application, indicating the occurrence of voltage-sensitive Na+ and K+ channels on a-MSH neurons. Replacement of Na+ by impermeant choline ions from 95 to 60 mM did not alter K(+)-evoked a-MSH release. Conversely, dramatic reduction of the external Na+ concentration to 16 mM caused a robust increase of a-MSH secretion from hypothalamic neurons, likely through activation of the Na+/Ca2+ exchange system. These data indicate that the depolarizing effect of K+ results from direct activation of voltage-operated Ca2+ channels. The lack of effect of TEA on basal a-MSH release prompted us to investigate the possible involvement of chloride ions in the regulation of the spontaneous activity of a-MSH neurons. Substitution of Cl- for impermeant acetate ions did not affect basal or K(+)-evoked a-MSH release.(ABSTRACT TRUNCATED AT 250 WORDS)
Groupe de Recherche en Endocrinologie Moléculaire, Unité Affilée à l'INSERM, Université de Rouen, Mont-Saint-Aignan, France.
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Bunel
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Delbende
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Blasquez
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Jégou
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Vaudry
D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D002118:Calcium / Q000502:physiology; D002712:Chlorides / Q000502:physiology; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism; D015640:Ion Channel Gating / Q000187:drug effects*; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009118:Muscimol / Q000494:pharmacology; D010042:Ouabain / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012636:Secretory Rate / Q000187:drug effects; D012964:Sodium / Q000502:physiology; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D014701:Veratridine / Q000494:pharmacology; D000521:alpha-MSH / Q000378:metabolism*
D002712:Chlorides; D007473:Ion Channels; D013757:Tetraethylammonium Compounds; D009118:Muscimol; D013779:Tetrodotoxin; D000521:alpha-MSH; D010042:Ouabain; D019789:Tetraethylammonium; D014701:Veratridine; D012964:Sodium; D015761:4-Aminopyridine; D011188:Potassium; D002118:Calcium; D001640:Bicuculline