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

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-HT4 receptor agonist, metoclopramide. Circular muscle preparations were electrically field-stimulated (EFS) to evoke cholinergically mediated contractions. Metoclopramide 10-100 mu M facilitated EFS-evoked contractions in forestomach (n=5-11,P<0.05); 1 mM inhibited. Metoclopramide had no effects in colon, apart from 100 mu M which reduced contractions. Prokineticin-2 0.001 nM-0.1 mu M (n=3-7) or [Nle(13)]-motilin 0.1 nM-1 mu M (n=4-8) had no effects in forestomach or colon. Ghrelin 0.01-1 mu M 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. (c) 2005 Elsevier B.V. All rights reserved.