Nitric oxide and carbon monoxide act as inhibitory neurotransmitters in the longitudinal muscle of C57BL/6J mouse distal colon

The present study was designed to identify the inhibitory neurotransmitters mediating nonadrenergic noncholinergic relaxation in the longitudinal muscle of c57/bl mouse distal colon. relaxation induced by electrical field stimulation (efs) was recorded isotonically in the presence of atropine and guanethidine. cyclic guanosine-3′,5′-monophosphate (cyclic gmp) content was measured by radioimmunoassay. efs-induced relaxation was inhibited by nitro-l-arginine ( l-nna) and sn (iv) protoporphyrin dichloride ix (snpp-ix),a nitric oxide (no) and carbon monoxide (co) synthase inhibitor,respectively. a combination of both inhibitors produced an additive effect. odq,a soluble guanylate cyclase inhibitor,inhibited efs-induced relaxation. nor-1,a no donor,and carbon monoxide-releasing molecule-2 (corm-2),a co donor,treatment relaxed the distal colon and increased cyclic gmp content. the effects of nor-1 and corm-2 were inhibited by odq. kt5823,a cyclic gmp-dependent protein kinase inhibitor,inhibited efs-induced relaxation. efs-induced relaxation in the presence of kt5823 was further inhibited by l-nna,but not by snpp-ix. in addition,kt5823 inhibited corm-2-induced relaxation,but not nor-1-induced relaxation. h89,a cyclic amp-dependent protein kinase inhibitor,inhibited efs-induced relaxation,and efs-induced relaxation in the presence of h89 was further inhibited by l-nna. these results suggested that no and co function as inhibitory neurotransmitters in the longitudinal muscle of c57bl mouse distal colon. ©2010 the japanese pharmacological society.