PITUITARY ADENYLATE-CYCLASE ACTIVATING POLYPEPTIDE (PACAP) AND VASOACTIVE-INTESTINAL-PEPTIDE STIMULATE 2 SIGNALING PATHWAYS IN CHO CELLS STABLY TRANSFECTED WITH THE SELECTIVE TYPE-I PACAP RECEPTOR

The properties of the pituitary adenylate cyclase activating polypepti de (PACAP) type I receptor were studied on a clone of Chinese hamster ovary cells (CHO) stably transfected with the recombinant receptor. PA CAP(1-27), PACAP(1-38) and VIP inhibited [I-125-acetyi-His(1)]PACAP(1- 27) binding, stimulated cyclic AMP and inositol phosphates production and induced [Ca2+](i) increase with the same order of potency: PACAP(1 -27)=PACAP(1-38) > VIP. The concentrations required for half maximal r eceptor occupancy, IP3- and [Ca2+](i) increase were not different for both PACAPs (1 nM) and 100-fold higher than those required for cyclic AMP increase (0.010 nM). These data suggest that the occupancy of a po rtion of the total receptors available was sufficient for maximal cycl ic AMP production but not for maximal IP3 production. It is concluded that the possibility of the type I PACAP receptor being coupled to a t ransduction pathway is not located at the level of the ligand but rath er at the level of the G-proteins.