Inhibition of neural nitric oxide synthase attenuates the chloride secretory response to stroking in human jejunum.

Abstract

Stroking of human jejunal mucosa induces serotonin release and a rise in short-circuit current (DeltaI(sc)). Nitric oxide is known to function as a nonadrenergic, noncholinergic neurotransmitter in response to neural serotonin receptor activation in the rat. We hypothesize that neural nitrergic mechanisms mediate the chloride secretory response to mucosal stroking in human jejunum. Segments of normal proximal jejunum were obtained from patients having gastric bypass surgery for obesity. Muscle-stripped segments of jejunum were mounted in Ussing chambers under short-circuit conditions. The neural nitric oxide synthase inhibitor, l-thiocitrulline, was added to experimental tissues. Mucosal stroking of control and experimental segments was then performed. Pretreatment with l-thiocitrulline attenuated the short circuit rise seen after stroking in the experimental group when compared with the control (5.4 +/- 1.5 microA/cm(2) vs 8.0 +/- 1.6 microA/cm(2); P <.05, Student t test, paired data, n = 11), but did not affect baseline I(sc) before stroking. Serotonin released by stroking was not different in experimental versus control tissue. The significantly reduced DeltaI(sc) in the group pretreated with the neural nitric oxide synthase inhibitor suggests that nitric oxide liberated from enteric neurons participates in the chloride secretory response to stroking in human jejunum in vitro.