PITUITARY ADENYLATE CYCLASE-ACTIVATING PEPTIDE STIMULATES CYCLIC-AMP ACCUMULATION IN UMR-106 OSTEOBLAST-LIKE CELLS

Pituitary adenylate cyclase-activating peptide (PACAP) and vasoactive intestinal peptide (VIP) share 68% homology and function as neurotrans mitters or neuroendocrine factors. Although VIP immunoreactivity has b een detected in bone cells, the presence of PACAP or PACAP receptors i n bone has not been determined. In this study, we investigated the rol e of PACAP and VIP in regulating cAMP accumulation in the UMR 106 oste oblast-like tumor cell line. PACAP 27 (10(-9) to 3 x 10(-7) M), PACAP 38 (10(-9) to 3 x 10(-7) M) and VIP (10(-8) to 10(-6) M) stimulated cA MP accumulation up to eightfold. PACAP 27 was slightly more potent tha n PACAP 38, and both were tenfold more potent than VIP. Both PACAP- an d VIP-stimulated cAMP accumulation were potentiated by 4 beta-phorbol 12-myristate 13-acetate, an activator of protein kinase C. Two PACAP a ntagonists, PACAP 6-27 (3 x 10(-6) M) and PACAP 6-38 (3 x 10(-6) M), b locked PACAP- and VIP-stimulated cAMP accumulation. Two VIP antagonist s ([Lys(1), pro(2,5), Arg(3,4), Tyr(6)]-VIP, and [4 Cl-D-Phe(6), Leu(1 7)]-VIP) did not reduce the PACAP- or VIP-stimulated cAMP accumulation . Pretreatment with PACAP 27, PACAP 38 or VIP equally blocked PACAP- a nd VIP-stimulated cAMP accumulation. These results suggest that PACAP is a more potent stimulator of cAMP accumulation than VIP in UMR 106 c ells. PACAP and VIP may share a role in the paracrine or neuroendocrin e regulation of bone metabolism.