PACAP-induced plasma extravasation in rat skin.

The effects of pituitary adenylate cyclase activating peptide (PACAP) 38, PACAP 27 and vasoactive intestinal peptide (VIP) on plasma extravasation were investigated in vivo in rat skin. PACAP 38, PACAP 27 and VIP, caused concentration-dependent extravasation in rat skin. The order of potency was PACAP 38 > PACAP 27 = VIP, whereas the order of maximal induced extravasation was PACAP 38 = PACAP 27 > VIP, suggesting that PACAP 38 might be the most powerful inducer of plasma extravasation of the three tested members of the secretin-glucagon-VIP family. Substance P (SP) was about 5 times more potent than PACAP 38 and 15 times more potent than PACAP 27. These data indicate that PACAP 38 induced plasma extravasation in concentrations roughly equimolar to SP. Pyrilamine (H1 receptor antagonist) reduced the PACAP 38-induced plasma extravasation more than 50%; cimetidine (H2 receptor antagonist) was without effect. To investigate whether a cAMP-mediated process is involved in the induction of plasma extravasation, the synthetic adenosine 3',5'-cyclic monophosphate (cAMP), dibutyryl adenosine cyclic monophosphate (DBcAMP) and the cAMP-inducing drug, salbutamol, were each injected in the skin; neither of these drugs caused extravasation. We conclude that PACAP 38 and PACAP 27 cause potent plasma extravasation which, at least in part, involves histamine release.