THE PITUITARY ADENYLATE-CYCLASE ACTIVATING POLYPEPTIDE (PACAP-I) AND VIP (PACAP-II VIP1) RECEPTORS STIMULATE INOSITOL PHOSPHATE SYNTHESIS IN TRANSFECTED CHO CELLS THROUGH INTERACTION WITH DIFFERENT G-PROTEINS

The PACAP receptor (PACAP I receptor, selective for PACAP) and the PAC AP II VIP1 receptor (recognizing PACAP and VIP with the same high affi nity) were stably expressed in Chinese Hamster Ovary (CHO) cells. Cell lines expressing different receptor densities, as measured by binding saturation curves, were selected. Inositol phosphate production was s timulated dose dependently in all the cell lines by PACAP and VIP, and the order of potency of the agonists was identical to that of high af finity receptor occupancy. The stimulatory effect of a saturating pept ide concentration was proportional to the total receptor density. At s imilar receptor densities, however, the PACAP receptor mediated stimul ation was higher than the VIP receptor-mediated stimulation. Pretreatm ent of the cells with pertussis toxin for 8 h had no effect on recepto r densities, did not alter the PACAP stimulated inositol phosphate syn thesis by the cells expressing the PACAP I receptor but markedly inhib ited the response of the cells expressing the PACAP II VIP1 receptor. Thus, the present results indicate that the two G(s)-coupled PACAP I a nd PACAP II VIP1 receptors may stimulate IP production. The maximal st imulation depended on the number of receptor expressed; the PACAP I an d PACAP II VIP1 receptors probably activated the phospholipase C throu gh G proteins of the G(q), and of the G(i)/G(0) families, respectively .