1698247

Effects of ions and ionic channel activators or blockers on release of alpha-MSH from perifused rat hypothalamic slices.

Article date: 1990/7/1

PubMed ID: 1698247

Journal name: Brain research. Molecular brain research (ISSN: 0169-328X)

ABSTRACT

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)

This document is available from: http://directlinks.cc/files/muscimol/1698247.pdf

Author List: Bunel D T, Delbende C, Blasquez C, Jégou S, Vaudry H

Publication Types: Journal Article; Research Support, Non-U.S. Gov't

Substances mentioned in the article: Chlorides; Ion Channels; Tetraethylammonium Compounds; Muscimol; Tetrodotoxin; alpha-MSH; Ouabain; Tetraethylammonium; Veratridine; Sodium; 4-Aminopyridine; Potassium; Calcium; Bicuculline;

Mesh terms: 4-Aminopyridine/pharmacology; Animals; Bicuculline/pharmacology; Calcium/physiology; Chlorides/physiology; Hypothalamus/drug effects; Ion Channel Gating/drug effects; Ion Channels/drug effects; Male; Membrane Potentials/drug effects; Muscimol/pharmacology; Ouabain/pharmacology; Potassium/pharmacology; Rats; Rats, Inbred Strains; Secretory Rate/drug effects; Sodium/physiology; Tetraethylammonium; Tetraethylammonium Compounds/pharmacology; Tetrodotoxin/pharmacology; Veratridine/pharmacology; alpha-MSH/secretion;

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