Possible role of orexin A in nonadrenergic, noncholinergic inhibitory response of muscle of the mouse small intestine

The effect of a novel peptide, orexin A, on longitudinal muscle of ICR mous e small intestine was examined in vitro. Exogenous orexin A induced a trans ient contraction in duodenal, jejunal and ileal segments. Atropine and tetr odotoxin completely inhibited the contractions. Contraction of longitudinal muscle of jejunal segments induced by electrical field stimulation was sti ll observed after the jejunal segment had been desensitized to orexin A, su ggesting that orexin A is not a final neurotransmitter to induce the contra ction. On the other hand, in the presence of atropine and guanethidine, ore xin A induced a transient gradual relaxation in duodenal, jejunal and ileal segments. Electrical field stimulation also induced significant relaxation of the muscle in jejunal segments. The electrical field stimulation-induce d relaxation was inhibited by 55% after the desensitization of the segments to orexin A. Although the electrical field stimulation-induced relaxation was inhibited by 47% by a nitric oxide synthesis inhibitor, NG-nitro-L-argi nine (L-NOARG), orexin desensitization did not affect the relaxation which persisted after L-NOARG treatment. The exogenous orexin A-induced relaxatio n was completely inhibited by L-NOARG. The results suggest that orexin A pa rtially mediates nonadrenergic, noncholinergic (NANC) relaxation via activa tion of nitrergic neurones in longitudinal muscle of ICR mouse small intest ine. (C) 2001 Elsevier Science B.V. All rights reserved.