AJP - Endocrinology and Metabolism, Vol 255, Issue 1 E59-E64, Copyright © 1988 by American Physiological Society
Calmodulin antagonist effects on GnRH and secretogogue-induced release of bovine LH
J. P. Kile and M. S. Amoss Jr
Department of Veterinary Physiology and Pharmacology, College of Veterinary Medicine, Texas A&M University, College Station 77843.
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.
