ANGIOTENSIN-II EFFECTS ON 2ND-MESSENGERS INVOLVED IN PROLACTIN SECRETION ARE MEDIATED BY AT(1)-RECEPTOR IN ANTERIOR-PITUITARY-CELLS

The two forms of angiotensin II (Ang II) receptors, AT(1) and AT(2) su btypes, have been demonstrated in many other cells beside the anterior pituitary cells. Attempting to investigate the subtype(s) of Ang II r eceptors implicated in the multiple transduction mechanisms involved i n Ang II stimulation of prolactin (PRL) release by lactotropes, we stu died the effect of selective nonpeptidergic Ang II antagonists on the PRL release, adenylate cyclase (AC), and phospholipase C activities. I n intact cells, the AT(1) antagonist DuP(753) blocked Ang II-induced P RL release, reversed in a dose dependent manner Ang II-evoked inositol phosphates production, and inhibited completely the PLC and protein k inase C (PKC) dependent cAMP accumulation induced by Ang II. In membra ne preparations, the Ang II receptors were negatively coupled to AC. T he AT(1) antagonist blocked in a dose dependent manner the inhibitory effect of Ang II on cAMP production. In intact cells, the negative cou pling of Ang II receptor with AC was observed only when PKC was down r egulated by long term 12-O-tetradecanolylphorbol-13-acetate pretreatme nt. Ang II was able to inhibit vaseactive intestinal peptide-induced c AMP accumulation, a response which was also prevented by DuP(753). The different coupling of Ang II receptor described above implicated only the AT(1) type receptor since the AT(2) antagonists (PD123177 and PD1 23319) were ineffective at any doses tested (10(-8) to 10(-5) M). The obtained results indicate that the regulation of PRL secretion involve s the AT(1) receptor subtype and that this receptor might be coupled t o multiple effecters. (C) 1994 Academic Press, Inc.