Serotonin neural receptors mediate motilin-induced motility in isolated, vascularly perfused canine jejunum.

We previously reported that motilin induced both motility and endoluminal release of serotonin (5-HT) in canine jejunum. The motility response was blocked by nonspecific tachyphylaxis of 5-HT receptors. In this study, we investigated the effect of a selective neural serotonin receptor (5-HT3) antagonist, ICS 205-930, given into either the artery or the lumen, on motilin-induced motility. Segments of canine jejunum were arterially perfused with Kreb's HCO3 solution containing 15% RBCs in an organ preservation system. Following a 15-min basal period (Basal-1), 500 fM motilin was infused into the artery over 15 min (Motilin-1). After a 30-min rest, the cycle was repeated (Basal-2 and Motilin-2) in the presence and absence (control) of ICS 205-930, which was given as a continuous infusion either into the artery or into the lumen (0.1 to 1.0 microM). From continuous intraluminal pressure tracings, a motility index (MI) was calculated for 5- or 15-min periods from the product of the frequency and the mean amplitude of phasic waves for that period. In control segments, motilin reproducibly induced significant (P less than 0.05) increases in MI over basal levels during both Motilin-1 and Motilin-2. Arterial 0.1 microM ICS 205-930 abolished the motor response to rechallenge with motilin: 145 +/- 28 to 288 +/- 10 mm Hg (Motilin-1) versus 168 +/- 27 to 168 +/- 13 mm Hg (Motilin-2). An infusion of 1 microM ICS 205-930 into the lumen was required to inhibit the response. Thus, motilin-induced motility is mediated by neural 5-HT receptors. Since both arterial and luminal antagonist was effective, it is likely that 5-HT3 receptors on both myenteric plexus neurons and neurons in proximity to mucosal enterochromaffin cells mediate the motor response to motilin.