The dopamine agonist, PHNO ((+)-4-propyl-9-hydroxynaphthoxazine), inhibits cyclic adenosine 3',5'-monophosphate formation and prolactin release from anterior pituitary cells.
In cultured rat anterior pituitary cells incubated for 30-180 min, PHNO caused a concentration-dependent inhibition of prolactin release (IC50 approximately 0.5 nM) with maximal suppression at 5 nM. Forskolin increased cyclic adenosine 3',5'-monophosphate (cAMP) generation by stimulating adenylate cyclase and PHNO inhibited this effect with the same concentration profile as for inhibition of prolactin release. Inhibitory effects of 0.5 nM PHNO on prolactin release and cAMP generation were abolished by coincubation with 10 nM haloperidol, a D2 dopamine receptor antagonist. Within 30 min, 0.5 nM PHNO blunted the stimulation of prolactin release due to 10 nM thyrotropin-releasing hormone (TRH) or angiotensin II (AII). Thus, PHNO appears to activate the D2 dopamine receptor to inhibit the formation of cAMP and the secretion of prolactin.
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I S
IS
Department of Neurology, University of Virginia School of Medicine, Charlottesville 22908.
Trugman
J M
JM
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001971:Bromocriptine / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis*; D018492:Dopamine Antagonists; D005260:Female; D006220:Haloperidol / Q000494:pharmacology; D066298:In Vitro Techniques; D010078:Oxazines / Q000494:pharmacology*; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000378:metabolism*; D011388:Prolactin / Q000097:blood / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology
D018492:Dopamine Antagonists; D010078:Oxazines; D000804:Angiotensin II; D005576:Colforsin; C042631:naxagolide; D001971:Bromocriptine; D013973:Thyrotropin-Releasing Hormone; D011388:Prolactin; D000242:Cyclic AMP; D006220:Haloperidol