Calmodulin antagonist effects on GnRH and secretogogue-induced release of bovine LH.
A study was performed to determine the possible role of calmodulin (CaM) in regulating gonadotropin-releasing hormone (GnRH)-induced luteinizing hormone (LH) release from the bovine pituitary using three structurally unrelated calmodulin antagonists. Primary calf anterior pituitary cell cultures (3 X 10(5)/well) were treated with either LH secretogogue (GnRH, 100 ng/ml; A23187, 2.5 microM; theophylline, 1 mM; prostaglandin E2, 1 microM; estradiol, 25 ng/ml; or KCl, 25 mM; final concentrations) or secretogogue plus CaM inhibitor in 1 ml Hanks' balanced salt solution plus 10 mM N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid for 6 h. Significant (P less than 0.01) inhibition of GnRH- and A23187-stimulated LH release was obtained with calmidazolium (CMZ; 1-10 nM) and N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7; 1-10 microM). Both CMZ (10 nM) and W-7 (10 microM) significantly reduced (P less than 0.05) LH release by all of the other agents tested as well. In contrast, trifluoperazine (TFP; 0.1-100 microM) had no effect against most of the secretogogues tested. These results suggest that GnRH-stimulated LH release is in part a Ca2+-CaM-dependent process and may implicate a common CaM-dependent mechanism for LH release in general. The data also demonstrate a marked dichotomy in response between the phenothiazine, TFP, and other CaM antagonists in the calf pituitary.
D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002147:Calmodulin / Q000037:antagonists & inhibitors*; D002417:Cattle; D015232:Dinoprostone; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology*; D007093:Imidazoles / Q000494:pharmacology; D007986:Luteinizing Hormone / Q000378:metabolism*; D008297:Male; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000378:metabolism; D011458:Prostaglandins E / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology; D014268:Trifluoperazine / Q000494:pharmacology
D002147:Calmodulin; D007093:Imidazoles; D011458:Prostaglandins E; D013449:Sulfonamides; D014268:Trifluoperazine; D007987:Gonadotropin-Releasing Hormone; D000001:Calcimycin; C031938:calmidazolium; C017967:W 7; D007986:Luteinizing Hormone; D015232:Dinoprostone