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 extrava sation were investigated in vivo in rat skin. PACAP 38, PACAP 27 and V IP, caused concentration-dependent extravasation in rat skin. The orde r 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. Substan ce P (SP) was about 5 times more potent than PACAP 38 and 15 times mor e potent than PACAP 27. These data indicate that PACAP 38 induced plas ma extravasation in concentrations roughly equimolar to SP Pyrilamine (H-1 receptor antagonist) reduced the PACAP 38-induced plasma extravas ation more than 50%; cimetidine (H-2 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'-c yclic 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 tha t PACAP 38 and PACAP 27 cause potent plasma extravasation which, at le ast in part, involves histamine release. (C) 1997 Elsevier Science B.V .