Effect of nedocromil sodium on non-adrenergic, non-cholinergic neural responses in guinea pig bronchi in vitro

Objective: Nedocromil sodium (nedocromil) improves the clinical condition o f asthmatic subjects but its mechanism of action is not fully understood. T his study aimed to determine whether nedocromil alters the ability of contr actile and relaxant non-adrenergic, non-cholinergic neural (NANC) responses to stabilise tone by inhibiting or potentiating these responses in bronchi al smooth muscle and, if so, whether the action is on a pre- or postjunctio nal level. Results: Nedocromil attenuated contractile but not relaxant NANC responses (elicited by electric field stimulation) significantly (P < 0.05 ) in guinea pig main bronchi in vitro. However, the ability of NANC respons es to stabilise tone (convergence effect) was not significantly impaired by nedocromil. Furthermore, nedocromil did not significantly shift the concen tration response curve (-log EC50) to neurokinin A (NKA). the dominating co ntractile NANC transmitter, or alter the maximum response to NKA (P > 0.05) . Submaximum or maximum contractile responses to histamine were not markedl y affected by nedocromil (P > 0.05). Conclusions: Nedocromil exerts selecti ve neural inhibition of the contractile but not of the relaxant NANC respon ses on a pre-junctional level in bronchial smooth muscle. Nedocromil does n ot, however, markedly impair the ability of NANC response to stabilise bron chial smooth muscle tone. (C) 1999 Elsevier Science B.V. All rights reserve d.