Nonadrenergic, noncholinergic responses of the human colon smooth muscle and the role of K+ channels in these responses.

The aim of the present study was to investigate the possible role of nitric oxide (NO) as a nonadrenergic, noncholinergic (NANC) mediator in human colon smooth muscle in vitro and to examine its possible interactions with K + channels. In the presence of atropine (10 -6 M) and guanethidine (10 5 M). electrical field stimulation (EFS, 1-10 Hz. 0.3 msec, 50 V) for 10 sec induced relaxations which were inhibited by tetrodotoxin (10 -6 M). In the presence of N G -nitro-L-arginine methyl ester (L-NAME, 10 -4 M), relaxations induced by EFS at 1, 2, 4, 8 and 10 Hz were reduced by 38.7 ± 4.3, 31.5 ± 3.8, 54.3 ± 5.4, 59.8 ± 4.5 and 68.6 ± 5.3%, respectively. The relaxations inhibited by L-NAME were restored by the preincubation of L-arginine (L-ARG. 10 -3 M) at all frequencies tested. D-Arginine (D-ARG, 10 -3 M) had no effect. Tetraethylammonium (TEA, 10 -4 M) or glibenclamide (10 -6 M) significantly decreased the relaxations induced by EFS. Exogenously applied sodium nitroprusside caused concentration-dependent relaxation with maximum relaxation observed with 10 -3 M. TEA (10 -4 M) and glibenclamide (10 -6 M) significantly depressed the maximum response to sodium nitroprusside. In conclusion, our data indicate that NO is involved in NANC nerve-mediated relaxation in the human colon smooth muscle and the relaxant responses to endogenously released or exogenously applied NO are mediated, in part, by activation of calcium-dependent and ATP-sensitive K + channels.