The regulation of alpha-MSH release by GABA is mediated by a chloride-dependent [Ca2+]c increase in frog melanotrope cells.
In frog melanotrope cells, gamma-aminobutyric acid (GABA) induces a biphasic effect, i.e. a transient stimulation followed by a more sustained inhibition of alpha-MSH release, and both phases of the GABA effect are mediated by GABAA receptors. We have previously shown that the stimulatory phase evoked by GABAA receptor agonists can be accounted for by calcium entry. In the present study, we have investigated the involvement of the chloride flux on GABA-induced [Ca2+]c increase and alpha-MSH release. We show that GABA evokes a concentration-dependent [Ca2+]c rise through specific activation of the GABAA receptor. The GABA-induced [Ca2+]c increase results from opening of voltage-activated L- and N-type calcium channels, and sodium channels. Variations of the extracellular Cl- concentration revealed that GABA-induced [Ca2+]c rise and alpha-MSH release both depend on the Cl- flux direction and driving force. These observations suggest for the first time that GABA-gated Cl- efflux provokes an increase in [Ca2+]c increase that is responsible for hormone secretion.
European Institute for Peptide Research (IFRMP 23), Laboratory of Cellular and Molecular Neuroendocrinology, INSERM U413, University of Rouen, 76821 Mont-Saint-Aignan, France.
Laurence
L
Desrues
Hélène
H
Castel
Maria M
MM
Malagon
Hubert
H
Vaudry
Marie-Christine
MC
Tonon
D000818:Animals; D002118:Calcium / Q000378:metabolism* / Q000502:physiology; D002455:Cell Division / Q000502:physiology*; D002478:Cells, Cultured; D002712:Chlorides / Q000502:physiology*; D003600:Cytosol / Q000378:metabolism; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D008297:Male; D052717:Melanotrophs / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D011893:Rana esculenta; D013654:Taurine / Q000031:analogs & derivatives / Q000494:pharmacology; D000521:alpha-MSH / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D002712:Chlorides; D018755:GABA Agonists; D018756:GABA Antagonists; D013654:Taurine; D005680:gamma-Aminobutyric Acid; D000521:alpha-MSH; C001355:tramiprosate; D002118:Calcium