Nitric oxide is involved in the relaxant effect of capsaicin in the human sigmoid colon circular muscle

The relaxant effect of capsaicin (300 nM) has been studied on mucosa-free circular strips of the human sigmoid colon in vitro. The response of precontracted preparations to capsaicin (sub-maximal relaxation) was reduced by over 50% by the nitric oxide synthase inhibitor N-G-nitro-L-arginine (L-NOARG; 20 muM or 100 muM) or by the guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; 1 muM), but not by tetrodotoxin (1 muM) or the P-2 purinoceptor antagonist pyridoxal phosphate 6-azophenyl-2',4'-disulfonic acid (PPADS; 50 muM). L-NOARG or ODQ caused moderate contraction of the circular muscle, indicating a tonic "nitrergic" control. Anandamide (1-100 muM), an endogenous cannabinoid and capsaicin VR1 receptor stimulant, failed to either mimic or modify the response to capsaicin (300 nM). It is proposed that capsaicin causes the release of smooth muscle relaxant substance(s) from afferent nerve endings in the gut wall, in a tetrodotoxin-resistant manner. Nitric oxide (possibly released from capsaicin-sensitive afferents) plays an important role in the capsaicin-evoked response. No evidence has been found for an involvement of PPADS-sensitive P-2 purinoceptors in the response to capsaicin or for a stimulation or inhibition of capsaicin-sensitive receptors by anandamide in the human sigmoid colon.