cAMP regulation of vasopressin mRNA content in hypothalamo-neurohypophysial explants

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.