Pituitary adenylate cyclase activating polypeptide is a potent vasodilator and oedema potentiator in rabbit skin in vivo.
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 133Xe 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 alpha-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 less than 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 125I-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.
Warren
J B
JB
Department of Applied Pharmacology, National Heart & Lung Institute, London.
Larkin
S W
SW
Coughlan
M
M
Kajekar
R
R
Williams
T J
TJ
D000818:Animals; D001920:Bradykinin; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D004357:Drug Synergism; D004487:Edema / Q000139:chemically induced* / Q000503:physiopathology; D007213:Indomethacin / Q000494:pharmacology; D007457:Iodine Radioisotopes; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D009479:Neuropeptides / Q000494:pharmacology*; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D011817:Rabbits; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D012867:Skin / Q000098:blood supply; D014665:Vasodilator Agents / Q000494:pharmacology*; D014980:Xenon Radioisotopes
D007457:Iodine Radioisotopes; D009479:Neuropeptides; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D014665:Vasodilator Agents; D014980:Xenon Radioisotopes; D015740:Calcitonin Gene-Related Peptide; D001920:Bradykinin; D007213:Indomethacin