Analysis of gamma-aminobutyric acidB receptor function in the in vitro and in vivo regulation of alpha-melanotropin-stimulating hormone secretion from melanotrope cells of Xenopus laevis.
The activity of many endocrine cells is regulated by gamma-aminobutyric acid (GABA). The effects of GABA are mediated by GABAA and/or GABAB receptors. While GABAB receptors in the central nervous system have now been extensively characterized, little is known of the function and pharmacology of GABAB receptors on endocrine cells. In the amphibian Xenopus laevis, GABA inhibits the release of alpha MSH from the endocrine melanotrope cells through both GABAA and GABAB receptors. We have investigated the following aspects of the GABAB receptor of the melanotrope cells of X. laevis: 1) the pharmacology of this receptor, using antagonists previously established to demonstrate GABAB receptors in the mammalian central nervous system; 2) the relative contribution to the regulation of hormone secretion by the GABAA and GABAB receptors on melanotrope cells in vitro; and 3) the role of the GABAB receptor with respect to the physiological function of the melanotrope cell in vivo, i.e. regulation of pigment dispersion in skin melanophores in relation to background color. Our results demonstrate that phaclofen, 2-hydroxysaclofen, and 4-aminobutylphosphonic acid dose-dependently blocked the inhibition of alpha MSH release by GABAB receptor activation, but not by GABAA receptor activation. The GABAB receptor antagonist delta-aminovaleric acid appeared to be a selective agonist on the GABAB receptor of melanotrope cells. The inhibitory secretory response to a low dose of GABA (10(-5) M) was not affected by bicuculline, but was significantly reduced by phaclofen, indicating that at a low GABA concentration, the GABAB receptor mechanism would dominate in inhibiting the melanotrope cells. Different thresholds of activation may form the basis for differential action of GABA through both GABA receptor types. The tonic inhibition of alpha MSH release in animals adapted to a white background was not affected by 4-aminobutylphosphonic acid, indicating that the GABAB receptor is not (solely) involved in the in vivo inhibition of alpha MSH release in animals on a white background.
De Koning
H P
HP
Department of Animal Physiology, University of Nijmegen, The Netherlands.
Jenks
B G
BG
Roubos
E W
EW
D000818:Animals; D001418:Baclofen / Q000031:analogs & derivatives / Q000494:pharmacology*; D002082:Butylamines / Q000494:pharmacology; D058787:GABA-A Receptor Antagonists; D006706:Homeostasis; D066298:In Vitro Techniques; D007700:Kinetics; D009943:Organophosphorus Compounds / Q000494:pharmacology; D010477:Perfusion; D010904:Pituitary Gland, Posterior / Q000187:drug effects / Q000378:metabolism*; D011863:Radioimmunoassay; D011963:Receptors, GABA-A / Q000502:physiology*; D014982:Xenopus laevis; D000521:alpha-MSH / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D002082:Butylamines; D058787:GABA-A Receptor Antagonists; D009943:Organophosphorus Compounds; D011963:Receptors, GABA-A; C052329:phaclofen; C079360:4-aminobutylphosphonic acid; D005680:gamma-Aminobutyric Acid; D000521:alpha-MSH; D001418:Baclofen; C057491:2-hydroxysaclofen