Mechanism mediating nitric oxide-induced inhibition in human jejunal longitudinal smooth muscle

Background. Enteric neurotransmission is a complex process involving multip le neurotransmitters, including nitric oxide (NO). Our aim was to evaluate the role and mechanism(s) of action of NO in normal human jejunal longitudi nal smooth muscle. Methods. Transmural strips of normal human jejunum obtained from subjects u ndergoing gastric bypass were studied in organ chambers. Effects of exogeno us NO (7 x 10(-6) mol/L to 7 x 10(-5) mol/L) and electrical field stimulati on (nonspecific release of endogenous neurotransmitters) on spontaneous con tractile activity and on precontracted muscle strips (substance P, 10(-5) m ol/L) were evaluated in the presence and absence of the competitive NO synt hase inhibitor N-G-amino-L-arginine (L-NNA, 10(-3) mol/L) and the specific soluble guanylyl cyclase inhibitor 1H-[1,2,4]-oxadiazaolo-[4,3-a]-quinoxali n-1-one (ODQ 10(-5) mol/L and 10(-4) mol/L). Results. Exogenous NO dose-dependently inhibited spontaneous contractility and relaxed precontracted smooth muscle strips. The effects of NO were mark edly, attenuated or completely inhibited in the presence of ODQ Electric fi eld stimulation under nonadrenergic, noncholinergic conditions also inhibit ed spontaneous contractility and relaxed precontracted smooth muscle strips ; both of these effects were attenuated, but not completely inhibited, in t he presence of both ODQ and L-NNA. Conclusions. NO is an endogenous inhibitory neurotransmitter in human jejun al longitudinal smooth muscle, acting at least in part via a mechanism medi ated by guanylyl cyclase. Other (non-nilrergic) nonadrenergic, noncholinerg ic inhibitory neurotransmitters are likely active in this portion of the hu man gut.