Article date: February 2007
By: E M Jarvie, V J North Laidler, S Corcoran, A Bassil, G J Sanger in Volume 150, Issue 4, pages 455-462
Background and purpose:
Motilin or 5‐HT4 receptor agonists stimulate gastrointestinal motility. Differences in activity are suggested but direct comparisons are few. A method was devised to directly compare the gastric prokinetic activities of motilin, the motilin receptor agonist, erythromycin, and the 5‐HT4 receptor agonist, tegaserod.
Experimental approach:
Gastric prokinetic‐like activity was assessed by measuring the ability to facilitate cholinergically‐mediated contractions evoked by electrical field stimulation (EFS) in rabbit isolated stomach. Comparisons were made between potency, maximal activity and duration of responses.
Key results:
Rabbit motilin (r.motilin) 0.003–0.3μM, [Nle13]motilin 0.003–0.3μM, erythromycin 0.3–10μM and tegaserod 0.1–10μM caused concentration – dependent potentiation of EFS‐evoked contractions. The potency ranking was r.motilin = [Nle13]motilin > tegaserod > erythromycin. The Emax ranking was r.motilin = [Nle13]motilin = erythromycin > tegaserod. Responses to r.motilin and [Nle13]motilin faded rapidly (t1/2 9 and 11 min, respectively) whereas those to erythromycin and tegaserod were maintained longer (t1/2 24 and 28 min). The difference did not appear to be due to peptide degradation. A second application of [Nle13]motilin was excitatory after 60 min contact and fade of the initial response (responses to 0.03 and 0.1μM [Nle13]motilin were not different from those caused by the first application).
Conclusions and implications:
Prokinetic‐like activities of the 5‐HT4 agonist tegaserod and the motilin receptor agonists were compared by measuring changes in cholinergically‐mediated contractions. This novel approach highlighted important differences between classes (greater Emax of motilin, compared with tegaserod) and for the first time, within each class (short t1/2 for motilin, compared with erythromycin).
DOI: 10.1038/sj.bjp.0707118
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