Pivotal role of the interstitial cells of Cajal in the nitric oxide signaling pathway of rat small intestine - Morphological evidence

The nitric oxide (NO) signaling pathway is a major nonadrenergic-noncholine rgic transmitter mechanism in the enteric nervous system. Our aim was to lo calize the enzymes in question, i.e., neuronal nitric oxide synthase (nNOS) , soluble guanylate cyclase (sGC), and cGMP-dependent kinase type I (cGK-I) in rat small intestine by indirect immunofluorescence. nNOS staining was f ound in neurons of the myenteric plexus and in varicose nerve fibers mainly in the circular muscle layer. The cells positive for neurokinin-1 (NK-1) r eceptor and c-kit (interstitial cells of Cajal, ICC) in the deep muscular p lexus (DMP) did not show nNOS reactivity, but nNOS-positive nerve fibers we re directly adjacent to them. sGC was found in flattened cells surrounding myenteric ganglia (periganglionic cells, PGC), in ICC of the DMP, faintly i n smooth muscle cells (SMC), and in cells perivascularly scattered througho ut the circular muscle layer. cGK-I immunoreactivity was found abundantly i n PGC (which presumably are ICC), in ICC of DMP, in SMC of the innermost ci rcular and longitudinal muscle layers, but less intensively in the outer ci rcular layer. Weak cGK-I staining occurred in nerve cells within the myente ric and submucosal plexus. Conclusively the key enzymes of the NO signaling pathway are differentially distributed: Occurrence of nNOS exclusively in neurons and the presence of sGC and cGK-I predominantly in ICC suggest a se quence of neuronal NO release, activation of ICC, and consecutive smooth mu scle relaxation. ICC of the DMP seem to be the primary targets for neurally released NO.