Morphine-like action of enkephalin analog FK 33-824 on motility of the isolated rat colon.

Actions of the synthetic met-enkephalin analog FK 33-824 were compared to normorphine on intraluminal pressure of the isolated rat colon. Phasic and tonic contractions of isolated colonic segments in Ringer-Tyrode9s solution under standard conditions were measured by intraluminal perfusion manometry. FK 33-824 or normorphine induced substantial tonic contractions of colonic muscles which lasted about 6 min. The maximum tonic contraction occurred at 10(-5) M normorphine or 10(-6) M FK 33-824. Naloxone (10(-6) M) and Mr 2266 alone or in combination inhibited competitively the tonic contraction induced by FK 33-824 with a similar potency ratio, whereas 10(-6) M norepinephrine or 10(-8) M isoproterenol inhibited it noncompetitively. Tetrodotoxin (10(-6) M) counteracted tonic contractions due to FK 33-824 or normorphine in all parts of the undissected colon but only in the proximal segment of the dissected colon and enhanced it in the middle and distal colonic segment. Neither 10(-5) M atropine sulfate nor 10(-6) M methysergide interfered with the action of FK 33-824 or normorphine. FK 33-824 produced morphine-like motor actions in the isolated rat colon evidently by stimulation of opiate receptors, suggested to be located in nervous and muscular tissue in the proximal and solely in muscular tissue in the mid and distal colonic segment. The neural pathway stimulated by FK 33-824 or normorphine is not identified. The data suggest it to be noncholinergic, nonadrenergic and nonserotoninergic.