Inflammatory oedema induced by synergism between calcitonin gene-related peptide (CGRP) and mediators of increased vascular permeability.
The potent vasodilator calcitonin gene-related peptide (CGRP, human synthetic), when mixed with histamine and injected intradermally in the rabbit, induced a marked potentiation of local oedema. CGRP also potentiated oedema induced by other mediators of increased microvascular permeability in the rabbit; bradykinin, platelet-activating factor (Paf), C5a des Arg, N-formylmethionyl-leucyl-phenylalanine (FMLP) and leukotriene B4 (LTB4). Substance P alone, or mixtures of substance P and CGRP, failed to induce oedema in rabbit skin. In rat skin, however, substance P induced oedema and this was potentiated by CGRP. CGRP had a protracted potentiating action following intradermal injection in the rabbit. The time for half loss of activity for CGRP was 40.1 +/- 7.5 min compared to 18 +/- 1 min for prostaglandin E2 (PGE2). No loss of potentiating activity was detected after incubation of CGRP in rabbit plasma or blood for 60 min. We postulate that endogenous CGRP, if released locally from nerve endings, could have a marked enhancing effect on oedema induced by other mediators in an inflammatory reaction.
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Williams
D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D015740:Calcitonin Gene-Related Peptide; D002199:Capillary Permeability; D003182:Complement C5 / Q000031:analogs & derivatives; D015937:Complement C5a, des-Arginine; D015232:Dinoprostone; D004357:Drug Synergism; D004487:Edema / Q000139:chemically induced*; D006632:Histamine / Q000494:pharmacology; D007249:Inflammation / Q000139:chemically induced; D007271:Injections, Intradermal; D007975:Leukotriene B4 / Q000494:pharmacology; D008297:Male; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D010972:Platelet Activating Factor; D011458:Prostaglandins E / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D011917:Rats, Inbred Lew; D012867:Skin / Q000098:blood supply; D013045:Species Specificity; D013373:Substance P / Q000494:pharmacology
D003182:Complement C5; D015937:Complement C5a, des-Arginine; D009419:Nerve Tissue Proteins; D010972:Platelet Activating Factor; D011458:Prostaglandins E; D007975:Leukotriene B4; D013373:Substance P; D009240:N-Formylmethionine Leucyl-Phenylalanine; D006632:Histamine; D015740:Calcitonin Gene-Related Peptide; D015232:Dinoprostone; D001920:Bradykinin