Stimulatory effects of the synthetic enkephalin analogue FK 33-824 on colonic motor activity antagonized by naloxone.
Enkephalins inhibit guinea pig ileum contractions in vitro; in vivo they increase gastric contraction strength and small intestinal spike activity in dogs and stimulate tonic and phasic contractile activity of the human colon. This study investigated the question as to whether the stimulatory effect of the synthetic met-enkephalin analogue FK 33-824 on the human colon is antagonized by the narcotic antagonist naloxone. On 3 experimental days 12 healthy young males received in random order (a) 4 mg (subjects 1-6) or 10 mg (subjects 7-12) naloxone i.v. followed by 1 mg FK 33-824 i.m., (b) saline i.v. followed by 1 mg FK 33-824 i.m. and (c) saline i.v. followed by saline i.m. FK 33-824 following saline produced a rapid increase of tonic intraluminal pressure (mean increase: 9.9 +/- 2.5 SEM mmHg; P less than 0.001), an increase in contractions from 1.6 +/- 0.4 to 3.3 +/- 0.8 per min (P less than 0.001), a shift in the dominant frequency of rhythmic contractions from 1.0 +/- 2.5 to 2.5-3.5 cycles per min, an increase in the amplitude of contractions from 10.1 +/-0 2.1 to 15.0 +/- 3.2 mmHg (P less than 0.01), and in the sum of the amplitudes as an overall measure of contractile activity from 148.6 +/- 36.7 to 482.9 +/- 136.9 mmHg (P less than 0.01). All effects lasted for more than 70 min; peak changes occurred in the first 15 min and subsided slowly in intensity. The effects of FK 33-284 were greatly attenuated by premedication of 4 mg naloxone, and abolished, at least for 15-30 min, by 10 mg naloxone. Saline caused no changes. It is concluded that the stimulatory effects of FK 33-824 on human colonic motility are antagonized by naloxone.
D000328:Adult; D004336:Drug Antagonism; D004723:Endorphins / Q000494:pharmacology*; D004745:Enkephalins / Q000494:pharmacology*; D005769:Gastrointestinal Motility / Q000187:drug effects*; D006801:Humans; D008297:Male; D009270:Naloxone / Q000494:pharmacology*; D012119:Respiration / Q000187:drug effects
D004723:Endorphins; D004745:Enkephalins; D009270:Naloxone