Inhibitory transmission to the longitudinal muscle of the mouse caecum is mediated largely by nitric oxide acting via soluble guanylyl cyclase

Abstract

In this work we describe a region of mouse intestine, the caecum, in which inhibitory transmission to the longitudinal muscle is predominantly due to nitric oxide. In the presence of muscarinic receptor blockade, electrical stimulation of intramural nerves in the longitudinal muscle of the mouse caecum evoked a relaxation. The relaxation was reduced to about 25% of the control amplitude by the nitric oxide synthase inhibitor l-NMMA ( N G-methyl- l-arginine), but was unaffected by d-NMMA. In the presence of the nitric oxide scavenger oxyhaemoglobin, the relaxation was reduced to less than 10% of the control amplitude. In the circular muscle of the caecum and the longitudinal muscle of the ileum, colon and rectum, electrical field stimulation either evoked only small relaxations, or relaxations that were unaffected by l-NMMA. Nitric oxide synthase-containing neurons in the caecum were localized immunohistochemically using an antibody to neuronal nitric oxide synthase or with NADPH diaphorase histochemistry. Reactive nerve cell bodies were observed in the myenteric plexus, and varicose nerve fibres were present in the longitudinal and circular muscle layers of the caecum. The transduction mechanism of the nitric oxide-mediated relaxation in the longitudinal muscle of the caecum was examined using ODQ (1 H-[1,2,4]oxadiazolo[4,3,-α-]quinoxalin-1-one), a selective inhibitor of soluble guanylyl cyclase. ODQ abolished the relaxations induced by applied sodium nitroprusside (0.01–1 mM) and reduced the relaxation induced by electrical stimulation to about 40% of control values. However, ODQ reduced the relaxations induced by electrical stimulation to a lesser extent than l-NMMA. Hence, although the relaxation in this tissue mediated by NO (or an NO-related substance) is largely via soluble guanylyl cyclase, an action of NO on other targets cannot be ruled out.