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Pituitary adenylate cyclase activating polypeptide is a potent vasodilator and oedema potentiator in rabbit skin in vivo
Author(s) -
Warren J.B.,
Larkin S.W.,
Coughlan M.,
Kajekar R.,
Williams T.J.
Publication year - 1992
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1992.tb14336.x
Subject(s) - calcitonin gene related peptide , bradykinin , endocrinology , medicine , vasoactive intestinal peptide , vasodilation , chemistry , calcitonin , in vivo , neuropeptide , pituitary adenylate cyclase activating peptide , biology , receptor , microbiology and biotechnology
1 The effects of pituitary adenylate cyclase activating polypeptide (PACAP) on microvascular blood flow and plasma protein leakage were investigated in rabbit skin in vivo . 2 Intradermal injection of PACAP38, the 38 amino acid form of the peptide, caused a dose‐dependent increase in blood flow measured by a 133 Xe clearance technique. An equivalent increase in blood flow was induced by 10 −12 mol per site of PACAP38, 10 −12 mol per site of human α‐calcitonin gene‐related peptide (CGRP) and 10 −10 mol per site of vasoactive intestinal polypeptide (VIP). 3 The vasodilator activity of PACAP38 was not significantly different from that of the 27 amino acid form of the peptide, PACAP27, when measured with a laser Doppler flow meter, causing a 104 ± 14% compared with 110 ± 18% increase above basal blood flow at 10 −12 mol per site respectively. 4 At 10 −12 mol per site the effect of PACAP38 was longer lasting than that of CGRP. Blood flow remained significantly increased above control at 2 h with PACAP38 ( P < 0.05) whereas blood flow after intradermal CGRP had returned to control values by this time. 5 PACAP38 injected alone had no significant effect on microvascular leakage of 125 I‐labelled albumin. However, PACAP38 significantly potentiated bradykinin‐induced oedema where it was approximately 100 fold more potent than VIP. 6 Oedema potentiation induced by PACAP38 was not inhibited by indomethacin at a dose which did inhibit potentiation of bradykinin‐induced oedema by arachidonic acid. 7 PACAP38 is at least as potent as other peptides which have been postulated to be involved in the inflammatory response when tested in rabbit skin in vivo . PACAP may contribute to both the hyperaemia and oedema components of inflammation.