European Journal of Pharmacology, 124 (1986) 343 347 343 Elsevier PLASMA EXTRAVASATION INDUCED BY DYNORPHIN-(I-13) IN RAT SKIN LORIS A. CHAHL * and J.S. CHAHL Faculo: of Medicine, University of Newcastle, Newcastle, N.S.W. 2308. Australia Received 29 January 1986, accepted 4 March 1986 L.A. CHAHL and J.S. CHAHL, Plasma extravasation induced by dvnorphin-(1-13) in rat skin, European J. Pharmacol. 124 (1986) 343 347. The plasma extravasation response to dynorphin-(1-13) was investigated using the Evans blue dye leakage technique. Dynorphin induced plasma extravasation in rat and guinea-pig abdominal skin with a similar potency to substance P. In rat skin dynorphin, unlike substance P, produced its action entirely by release of histamine and 5-hydroxytryptamine since the response was abolished by pretreatment of rats with mepyramine and methysergide. Pretreatment of rats with capsaicin or the tachykinin antagonist, spantide, reduced but did not abolish the response to dynorphin, indicating that its action was not mediated primarily by a neurogenic mechanism. Since the response was not significantly reduced by naloxone it was concluded that the plasma extravasation response to dynorphin was mediated by receptors other than tt opiate receptors. Thus dynorphin, if released from sensory nerves, might play a role in neurogenic inflammation. Substance P antagonists Dynorphin Neurogenic inflammation Capsaicin Plasma extravasation Mast cell amines 1. Introduction The dynorphins are the most recently dis- covered opioid peptide family (Goldstein et al., 1981) and are derived from the pro-dynorphin molecule (see Weber et al., 1983). The 17 amino acid peptide, dynorphin A and its 13 amino acid counterpart contain the sequence of [LeuS]en- kephalin at the N-terminal and exhibit selective agonist activity at ~ opiate receptors (e.g. Yoshimura et al., 1982). Dynorphin has been reported to coexist with substance P (SP), calcitonin gene-related peptide (CGRP) and cholecystokinin (CCK) in primary afferent neurones in the skin and iris of guinea-pigs (Gibbins et al., 1985). Furthermore opioid peptides including dynorphin have been reported to cause mast cell degranulation and wheal-and-flare re- sponses in human skin (Casale et al., 1984). SP released from peripheral terminals of primary * To whom all correspondence should be addressed. 0014-2999/86/$03.50 ¢'~1986 Elsevier Science Publishers B.V. afferent neurones has been proposed to be the mediator of antidromic vasodilatation and neuro- genic plasma extravasation in the skin (Lembeck and Holzer, 1979) and satisfies some of the criteria for a major mediator of these phenomena (Per- now, 1983). The reported coexistence of dy- norphin with SP in. these neurones prompted the present study, using the commonly used Evans blue due leakage assay, to compare the cutaneous plasma extravasation response to dynorphin with that to SP and to determine whether there was any interaction between these two peptides. 2. Materials and methods Male and female Wistar rats, 150-250 g, were used. In individual experiments rats were matched for weight and sex in control and treatment groups. Equal numbers of control and treated rats were tested on each experimental day to avoid bias due to possible seasonal variations. They were anaesthetized with ether and given Evans blue 50