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 NG-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.
Sahin
A S
AS
Department of Pharmacology and Department of Pediatric Surgery, Faculty of Medicine, Selçuk University, Konya, Turkey. aysesaide@hotmail.com
Atalik
K E
KE
Günel
E
E
Dogan
N
N
D003106:Colon; D004347:Drug Interactions; D004558:Electric Stimulation; D006801:Humans; D009130:Muscle, Smooth / Q000187:drug effects*; D009569:Nitric Oxide / Q000494:pharmacology*; D010276:Parasympatholytics / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects* / Q000502:physiology
D010276:Parasympatholytics; D015221:Potassium Channels; D009569:Nitric Oxide