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Eur J Pharmacol. 2005 Nov 7;524(1-3):138-44. Epub 2005 Oct 19.

Prokineticin-2, motilin, ghrelin and metoclopramide: prokinetic utility in mouse stomach and colon.

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  • 1Neurology and Gastrointestinal Centre of Excellence for Drug Discovery, GlaxoSmithKline, New Frontiers Science Park, Harlow, UK.

Abstract

The ability of agents described as gastrointestinal prokinetics (prokineticin-2, [Nle(13)]-motilin, ghrelin), to modulate nerve-mediated contractions of mouse isolated stomach and colon was determined and compared with the prokinetic and 5-HT(4) receptor agonist, metoclopramide. Circular muscle preparations were electrically field-stimulated (EFS) to evoke cholinergically mediated contractions. Metoclopramide 10-100 microM facilitated EFS-evoked contractions in forestomach (n = 5-11, P < 0.05); 1 mM inhibited. Metoclopramide had no effects in colon, apart from 100 microM which reduced contractions. Prokineticin-2 0.001 nM-0.1 microM (n = 3-7) or [Nle(13)]-motilin 0.1 nM-1 microM (n = 4-8) had no effects in forestomach or colon. Ghrelin 0.01-1 microM facilitated EFS-evoked contractions in forestomach (n = 5-7, P < 0.05) but not in colon (n = 5-8). We conclude that ghrelin and metoclopramide facilitate excitatory nerve activity because neither affected inhibitory responses to EFS in the presence of atropine, or contractions to carbachol. Further, prokineticin-2 and [Nle(13)]-motilin are unlikely to exert gastric prokinetic activity in this species, the inactivity of the latter being consistent with an absence of the motilin receptor in rodents.

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