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Am J Physiol Regul Integr Comp Physiol 271: R554-R560, 1996;
0363-6119/96 $5.00
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AJP - Regulatory, Integrative and Comparative Physiology, Vol 271, Issue 3 554-R560, Copyright © 1996 by American Physiological Society


ARTICLES

cAMP regulation of vasopressin mRNA content in hypothalamo-neurohypophysial explants

C. D. Sladek, K. Y. Fisher, H. E. Sidorowicz and J. R. Mathiasen
Department of Physiology, Finch University of Health Sciences, Chicago Medical School, Illinois 60064, USA.

Stimulation of vasopressin (VP) gene expression by adenosine 3',5'-cyclic monophosphate (cAMP) has been observed in dispersed hypothalamic cultures, in VP-expressing cell lines, and in cells transfected with reporter genes regulated by the VP gene promoter. However, treatment of hypothalamo-neurohypophysial system (HNS) explants with forskolin (25 microM), an activator of adenyl cyclase, and 3-isobutyl-1-methylxanthine (IBMX; 500 microM), a phosphodiesterase inhibitor, resulted in a decrease in VP mRNA. Time course analysis revealed that IBMX and forskolin reduced the VP mRNA content to 50% of control explants after 8 and 12 h despite a dramatic stimulation of VP release. This effect was due to the activation of adenyl cyclase by forskolin, because neither IBMX alone nor the inactive analogue of forskolin, 1,9-dideoxyforskolin, decreased VP mRNA content. In contrast, 8-bromoadenosine 3',5'-cyclic monophosphate and the D1 dopamine receptor agonist, SKF-38393, increased VP mRNA content, but these agents were less potent in stimulating VP release, suggesting a concentration dependency of the forskolin effect. This was confirmed when forskolin (10 microM) was found to increase VP mRNA content. Thus receptor-mediated activation of adenyl cyclase results in an increase in VP mRNA content.


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