Motilin's induction of phasic contractility in canine jejunum is mediated by the luminal release of serotonin.

To determine whether mucosal serotonin (5-HT) is involved in the intestinal motility response to motilin, we studied the effects of intra-arterial infusions of motilin (5 X 10(-10) mol/L) in isolated, vascularly perfused segments of canine jejunum. Intraluminal pressures were continuously recorded through a perfused manometric catheter, and venous and luminal 5-HT levels were measured by radioimmunoassay. Luminal 5-HT output rose from a basal of 54 +/- 12 to a peak of 151 +/- 30 ng/min X 100 gm (p less than 0.01) with the motilin infusion. The earliest significant rise in luminal (5-HT), which occurred at 1 minute after the start of the motilin infusion, preceded the onset of phasic contractility. The rise in the motility index induced by motilin demonstrated a strong correlation (r = 0.72, p less than 0.01) with rises in luminal 5-HT output. 5-HT tachyphylaxis abolished the motility response to motilin; prior treatment with atropine abolished, while tetrodotoxin inhibited the luminal release of 5-HT. An infusion of exogenous 5-HT giving equivalent luminal 5-HT levels as induced by motilin led to similar phasic contractility and rise in the motility index. These findings suggest that motilin initiates phasic contractility in canine jejunum through the cholinergically mediated release of mucosal serotonin.