Studies on pituitary melanotrophs reveal the novel GABAB antagonist CGP 35-348 to be the first such compound effective on endocrine cells.

Article date: 1991/2/22

PubMed ID: 1676516

Journal name: Proceedings. Biological sciences (ISSN: 0962-8452)


One obstacle to understanding the action and physiological significance of the responsiveness of various endocrine cells to gamma-aminobutyric acid (GABA) has been that previously available substances, all active as GABAB antagonists in the nervous system, are ineffective on endocrine cells. The introduction of a potent new member of this class, CGP 35-348, of very different chemical structure, encouraged us to examine its effect on endocrine cells. For this purpose, we studied melanotroph secretion from pituitary neurointermediate lobes. We found that CGP 35-348, in contrast to previously available members of this class, suppressed completely, in rat and toad, secretory responses to baclofen, the classic GABAB agonist. Analysis, in toad, showed CGP 35-348 did not affect responses to GABAA agonists (muscimol; isoguvacine), dopamine, or neuropeptide Y. When tested against GABA, the physiological ligand present in the innervation of melanotrophs (along with dopamine and neuropeptide Y), CGP 35-348 completely suppressed the secretory response, which, in toad, is purely inhibitory and unaffected by bicuculline, the specific GABAA antagonist. In addition, CGP 35-348 unmasked a stimulant effect that bicuculline blocked. In CGP 35-348, we thus have a new tool with which to analyse responses to GABA and their physiological involvement in endocrine cells.

This document is available from: http://directlinks.cc/files/muscimol/1676516.pdf

Author List: Shibuya I, Kongsamut S, Douglas W W

Publication Types: Journal Article; Research Support, U.S. Gov't, P.H.S.

Substances mentioned in the article: GABA Antagonists; GABA-A Receptor Antagonists; Organophosphorus Compounds; Muscimol; CGP 35348; Melanocyte-Stimulating Hormones; Methionine; Baclofen; 2-hydroxysaclofen; Bicuculline;

Mesh terms: Animals; Baclofen/analogs & derivatives; Bicuculline/pharmacology; Darkness; GABA Antagonists; GABA-A Receptor Antagonists; Kinetics; Male; Melanocyte-Stimulating Hormones/biosynthesis; Methionine/metabolism; Muscimol/pharmacology; Organophosphorus Compounds/pharmacology; Pituitary Gland/drug effects; Rats; Rats, Inbred Strains; Xenopus laevis;

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