THE 2 FORMS OF THE PITUITARY ADENYLATE-CYCLASE ACTIVATING POLYPEPTIDE (PACAP-(1-27) AND PACAP-(1-38)) INTERACT WITH DISTINCT RECEPTORS ON RAT PANCREATIC AR-4-2J CELL-MEMBRANES

The existence of specific receptors for the two PACAPs (Pituirary Adenylate Cyclase Activating Peptides of 27 and 38 amino acids) was previously demonstrated on membranes from the pancreatic acinar cell line AR 4-2J (Buscail et al., FEBS Lett. 202, 77-81, 1990) by [I-125]PACAP-27 binding. Here we demonstrate, by comparing Scatchard analysis of saturation curves and competition binding curves obtained with [I-125]PACAP-27 and [I-125]PACAP-38 as radioligands, the coexistence of two classes of receptors : 1/ PACAP-A receptors that recognize PACAP-27 and PACAP-38 with the same high affinity (K(d) 0.3 nM) and 2/ PACAP-B receptors that recognize PACAP-38 with a high affinity (K(d) 0.3 nM) and PACAP-27 with a lower affinity (K(d) 30 nM). These two receptors are are coupled to adenylate cyclase but can be clearly distinguished by the ability of PACAP(6-27) to specifically inhibit PACAP-27 adenylate cyclase activation.