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

The ability of agents described as gastrointestinal prokinetics (prokineticin-2, [Nle13]-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 μM facilitated EFS-evoked contractions in forestomach (n = 5-11, P < 0.05); 1 mM inhibited. Metoclopramide had no effects in colon, apart from 100 μM which reduced contractions. Prokineticin-2 0.001 nM-0.1 μM (n = 3-7) or [Nle13]-motilin 0.1 nM-1 μM (n = 4-8) had no effects in forestomach or colon. Ghrelin 0.01-1 μM 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 [Nle13]-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.