Inhibition of prolactin release and blockade of adenohypophyseal cell cyclic AMP accumulation are two dissociable effects of dopaminergic and non-dopaminergic drugs.
The secretion of PRL by the anterior pituitary gland is under a tonic inhibitory control exerted by dopamine (DA). However, the mechanism(s) involved in the inhibition of PRL secretion is not clearly defined. Several recently published papers supported the hypothesis that DA inhibits the release of PRL through blockade of the pituitary adenylate cyclase-cyclic AMP system. We have recently demonstrated that sodium ions are essential for dopaminergic inhibitory action on PRL secretion. The present paper reports the effects, in the presence or in the absence of Na+, of either DA, bromocriptine, apomorphine or 2 anticalmodulin drugs, penfluridol and W-7, on cyclic AMP accumulation by rat adenohypophyseal cells in primary culture. Studies with dopaminergic agonists show that in the presence of Na+ inhibition of both PRL and cyclic AMP is obtained at 15 and 30 min, while in the absence of the ion a dissociation exists between the inhibition of PRL release which is completely abolished, and that of cyclic AMP content which is still present. Dose-response studies done in the presence of Na+ show the existence of a good correlation between hormone and nucleotide effects of dopaminergic agonists while, in the absence of Na+, a dissociation is observed between the inhibition of PRL release, which is completely suppressed, and that of cyclic AMP accumulation which is slightly or not at all decreased. The inhibitory effects of penfluridol after 15 and 30 min of incubation were not suppressed by Na+ removal, although its hormonal actions were slightly decreased.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001971:Bromocriptine / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism*; D004298:Dopamine / Q000494:pharmacology*; D005260:Female; D010903:Pituitary Gland, Anterior / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011388:Prolactin / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000378:metabolism; D013997:Time Factors
D001971:Bromocriptine; D011388:Prolactin; D012964:Sodium; D000242:Cyclic AMP; D001058:Apomorphine; D004298:Dopamine