NEURAL CONTROL OF MOUSE SMALL-INTESTINAL LONGITUDINAL MUSCLE - INTERACTIONS WITH INFLAMMATORY MEDIATORS

The present study was undertaken to investigate neural control of mous e small intestinal longitudinal muscle. Electrical field stimulation e voked acetylcholine- and neurokinin A-mediated contractile responses, whereas nitric oxide-mediated neuro-transmission resulted in relaxatio n. The inflammatory mediators, histamine and leukotriene D-4, contract ed the longitudinal muscle preparation. Histamine-evoked contractions resulted from binding to histamine H-1 receptors on non-neural cells o f the small intestine. Leukotriene D-4 played a role in neurokinin A-m ediated excitation as the leukotriene D-4 receptor antagonist, WY 48,2 52, reduced the response to nerve stimulation under noncholinergic con ditions by almost 80%. In contrast, WY 48,252 had no effect on the res ponse to exogenous neurokinin A, indicating that the response to this neurotransmitter is not mediated by leukotriene D-4 release. Subthresh old concentrations of leukotriene D-4 did not modify the response to n eurokinin A, ruling out a synergistic relationship between these two a gonists. Leukotriene D-4 did not cause synaptic transmitter release th rough ganglionic stimulation, because its contractile effect was tetro dotoxin insensitive, and did not contribute to noncholinergic excitati on through stimulation of neurokinin A release, as the neurokinin(2) r eceptor antagonist, MEN 10,376, did not alter the response to leukotri ene D-4. instead leukotriene D-4 may modulate the release of neurokini n A from nerve endings during nerve stimulation.