THE MODULATION OF INFLAMMATORY EDEMA BY CALCITONIN GENE-RELATED PEPTIDE

1 The effect of calcitonin gene-related peptide (CGRP) when given with or as a pretreatment to oedema inducing agents was investigated in the skin and paws of male Wistar and Sprague Dawley rats. 2 Oedema formation at intradermally-injected sites in the skin was measured by a I-125-labelled human serum albumin accumulation technique and paw oedema was measured by a weight displacement technique. 3 CGRP (30 pmol) when given with, or as a 20 min pretreatment, markedly potentiated oedema formation induced by substance P (100 pmol) in rat skin. In comparison, CGRP had little effect on 5-hydroxytryptamine (5-HT, 0.1 - 3 nmol)-induced oedema when given as a co-injection but significantly potentiated 5-HT-induced oedema when given as a 20 min pretreatment in the skin. Similar results were obtained in both Wistar and Sprague Dawley rats. 4 Pretreatment with CGRP (30 pmol) had little modulatory effect on oedema induced by substance P (100 pmol) in the presence of the vasodilator prostanoid, prostaglandin E1 (PGE1, 850 pmol) in the skin of Wistar rats. 5 Pretreatment with CGRP (30 pmol) caused a non-significant increase in carrageenin (300 mug)-induced oedema in the hind paw of Wistar rats. Capsaicin (100 nmol) given as a pretreatment had little effect on carrageenin-induced oedema. 6 CGRP (30 pmol), given as a pretreatment, had little modulatory effect on 5-HT (3 nmol)-induced oedema in the paw of Wistar rats but a non-significant decrease in paw oedema was observed in Sprague Dawley rats. 7 The results suggest that CGRP, either given together with or as a pretreatment to mediators of increased microvascular permeability, depending on circumstance, can act in a synergistic manner to increase oedema formation. Little evidence was obtained for an anti-inflammatory effect of CGRP in either the rat skin or paw.