MODULATION OF THE RELEASE AND ACTIVITY OF NEUROPEPTIDES IN THE MICROCIRCULATION

Electrical stimulation of the sensory saphenous nerve leads to neuroge nic edema formation in the innervated area of the paw of the anestheti zed rat. Evidence suggests that the edema formation is the result of i ncreased microvascular permeability mediated via neurokinin NK1 recept ors and increased blood flow mediated via calcitonin gene related pept ide CGRP(1) receptors. Results indicate that selective receptor antago nists will only inhibit the response mediated by the specific receptor they antagonise. In the case of neurogenic inflammation, where it is common for more than one biologically active neuropeptide to be releas ed concomitantly, it may be more sensible to develop agents that inhib it neuropeptide release. The effects of some agents suggested to affec t neurogenic responses are presented. The anti-inflammatory steroid de xamethasone (1 mg/kg subcutaneously, -4 h) significantly (p < 0.01) in hibited edema formation, but the mechanism of action is likely to be r elated to the general anti-edema effect of dexamethasone. In contrast the anti-asthma agent nedocromil sodium (up to 10 mg/kg intravenously, -15 min) and the histamine H-3 agonist (R)-alpha-methyl histamine (1- 10 mg/kg intravenously, -5 min) both failed to inhibit saphenous nerve induced edema formation, despite positive results in other sensory ne rve systems. The results are discussed in the context of evidence obta ined using other agents in skin.