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.
Sladek
C D
CD
Department of Physiology, Finch University of Health Sciences, Chicago Medical School, Illinois 60064, USA.
Fisher
K Y
KY
Sidorowicz
H E
HE
Mathiasen
J R
JR
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000818:Animals; D005576:Colforsin / Q000494:pharmacology; D046508:Culture Techniques; D000242:Cyclic AMP / Q000502:physiology*; D018491:Dopamine Agonists / Q000494:pharmacology; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009994:Osmolar Concentration; D010904:Pituitary Gland, Posterior / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013268:Stimulation, Chemical; D013997:Time Factors; D014667:Vasopressins / Q000235:genetics*
D018491:Dopamine Agonists; D012333:RNA, Messenger; D014667:Vasopressins; D005576:Colforsin; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D000242:Cyclic AMP