C-terminally shortened pituitary adenylate cyclase-activating peptides (PACAP) discriminate PACAP I, PACAP II-VIP1 and PACAP II-VIP2 recombinant receptors.

Pituitary adenylate cyclase-activating polypeptide (PACAP) analogues were tested for their ability to occupy the recombinant selective PACAP receptors (PACAP type I receptors) and the non-selective PACAP-vasoactive intestinal polypeptide (VIP) receptors (PACAP type II, VIP1 and PACAP type II, VIP2 receptors), stably transfected and expressed in Chinese hamster ovary cells. Their capacity to stimulate the adenylate cyclase activity was also measured. The synthetic analogues tested were peptides shortened at the carboxyl terminus by the removal of 1-4 amino acids (PACAP-26 to PACAP-23). All the peptides discriminated the 3 receptor subtypes and had the highest affinity for the VIP1 receptors, and the lowest affinity for the VIP2 receptors; PACAP-25 having the highest ability to discriminate the VIP1 and VIP2 receptors. All the peptides tested were full agonists on the PACAP I and VIP1 receptors; PACAP-25 and -26 were partial agonists on VIP2 receptors and may be appropriate tools to establish the receptor subtype involved in a given cellular response.