NONADRENERGIC, NONCHOLINERGIC RELAXATION IN LONGITUDINAL MUSCLE OF RAT JEJUNUM

The mediators of nonadrenergic, noncholinergic (NANC) relaxation in th e longitudinal muscle of rat jejunum were studied in vitro. Electrical field stimulation (EFS) of segments of rat jejunum induced a rapid tr ansient relaxation followed by a subsequent contraction in the presenc e of atropine and guanethidine. N-G-Nitro-L-arginine (L-NOARG, 10 mu M ) inhibited the EFS-induced NANC relaxation by about 25%, and L-argini ne (1 mM) completely reversed this inhibition. Exogenously added nitri c oxide (0.1-10 mu M) induced relaxation of the segment. Treatment of the segment with a-chymotrypsin resulted in about 50% inhibition of th e EFS-induced relaxation. Several peptide candidates for the mediator of NANC relaxation were examined by using selective antagonists of the ir receptors or by a receptor-desensitization method. Results indicate d that vasoactive intestinal peptide, pituitary adenylate cyclase acti vating peptide, peptide histidine isoleucine, atrial natriuretic pepti de and neurotensin are not associated with NANC relaxation of the segm ents. On the other hand, apamin at 1 mu M inhibited the EFS-induced re laxation by 74%. Inhibitory effects of L-NOARG and, apamin or alpha-ch ymotrypsin treatment on the EFS-induced relaxation were additive and a lmost complete. Exogenous nitric oxide-induced relaxation was not affe cted by apamin. Inhibitory junction potentials (i.j.p.'s) were recorde d from longitudinal muscle cells of rat jejunum. Apamin at 200 nM abol ished i.j.p.'s induced by two pulses of EFS. These results suggest tha t NANC relaxation in longitudinal muscle of rat jejunum involves two i ndependent components: one is a nitric oxide-mediated minor component, and the other is an unknown substance-mediated apamin-sensitve major component that is inhibited by alpha-chymotrypsin treatment.