The GABA(B) antagonist CGP 52432 attenuates the stimulatory effect of the GABA(B) agonist SKF 97541 on luteinizing hormone secretion in the male sheep.
The objectives of this study were to determine if the gamma-aminobutyric acid (GABA)(B) agonist, 3-aminopropyl (methyl) phosphinic acid (SKF97541), would increase luteinizing hormone (LH) secretion when infused by microdialysis into the medial basal hypothalamus (MBH) of the castrated ram, and to determine if the action of SKF97541 would be attenuated by co-infusion of the GABA(B) antagonist CGP52432. Initial experiments established that infusion of SKF alone, at concentrations as low as 5 microM, increased mean LH, LH pulse amplitude, and in some cases, pulse interval. In the last experiment, animals were treated with artificial cerebrospinal fluid (CSF) alone, SKF alone (30 microM), 3-[[(3, 4-dichlorophenol) methyl] amino] propyl] diethoxymethyl) phosphinic acid (CGP) alone (500 microM), or SKF plus CGP. SKF increased both mean LH and LH pulse amplitude as compared with CSF. CGP alone had no significant effect on LH, but it attenuated the effect of SKF on mean LH. These observations indicate that the stimulatory effects of GABA(B) agonists on LH pulse patterns are mediated through GABA(B) receptors and provide further evidence that GABA(B) receptors located in the MBH can regulate pulsatile GnRH-LH release.
Jackson
Gary L
GL
Department of Veterinary Biosciences, University of Illinois, 2001 West Lincoln Avenue, 3838 VMBSB, Urbana, IL 61802, USA. g.jackson@uiuc.edu
Kuehl
David
D
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001596:Benzylamines / Q000494:pharmacology*; D002369:Castration; D004305:Dose-Response Relationship, Drug; D018756:GABA Antagonists / Q000494:pharmacology*; D058786:GABA-B Receptor Agonists; D058788:GABA-B Receptor Antagonists; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D007986:Luteinizing Hormone / Q000378:metabolism*; D008297:Male; D017551:Microdialysis; D009943:Organophosphorus Compounds / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D010721:Phosphinic Acids / Q000494:pharmacology*; D018080:Receptors, GABA-B / Q000378:metabolism; D012756:Sheep
D001596:Benzylamines; D018756:GABA Antagonists; D058786:GABA-B Receptor Agonists; D058788:GABA-B Receptor Antagonists; D009943:Organophosphorus Compounds; D010721:Phosphinic Acids; D018080:Receptors, GABA-B; C068457:3-aminopropyl(methyl)phosphinic acid; C083008:CGP 52432; D007986:Luteinizing Hormone