MMQ cells: a model for evaluating the role of G proteins in the modulation of prolactin release.

It is well known that dopamine (DA) inhibits while vasoactive intestinal peptide (VIP) and angiotensin II (ANG II) stimulate prolactin (PRL) release from normal anterior pituitary lactotrophs; however, elucidation of the intracellular mechanisms involved in these effects has been hindered by the cellular heterogeneity of the anterior pituitary. MMQ cells, isolated from the PRL-secreting rat pituitary tumor 7315a is an interesting model since they only secrete PRL. In order to determine whether and which GTP-binding (G) proteins are involved in the modulation of cyclic 3',5'-adenosine monophosphate (cAMP) accumulation and phospholipids turnover and eventually PRL release, we have performed studies with MMQ cells. For this purpose, the levels of various G proteins (alpha o, alpha s, alpha i, alpha q and beta) and their mRNAs, measured by Western and Northern blots respectively, were correlated with intracellular cAMP accumulation in response to DA, VIP or DA plus VIP, and with inositol phosphates (IPx) formation in response to ANG II, DA or DA plus ANG II. This study shows that, when compared to normal pituitary tissue, the levels of alpha o, alpha o2 and alpha i3 were significantly decreased in MMQ cells; those of alpha o1, alpha i (alpha i1 + alpha i2), alpha s42 and alpha q were very low or undetectable while those of alpha s47 and beta were normal. DA was unable to inhibit basal PRL release and cAMP accumulation. VIP increased both cAMP accumulation and PRL release, while cAMP accumulation elicited by VIP could be suppressed by DA. BAY K 8644-induced PRL release also could be suppressed by DA.(ABSTRACT TRUNCATED AT 250 WORDS)