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-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.
Bassil
Anna K
AK
Neurology and Gastrointestinal Centre of Excellence for Drug Discovery, GlaxoSmithKline, New Frontiers Science Park, Harlow, UK.
Dass
Narinder B
NB
Murray
Charles D
CD
Muir
Alison
A
Sanger
Gareth J
GJ
D000818:Animals; D003106:Colon / Q000187:drug effects / Q000294:innervation / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005768:Gastrointestinal Hormones / Q000494:pharmacology*; D054439:Ghrelin; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008787:Metoclopramide / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D009037:Motilin / Q000031:analogs & derivatives / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects*; D009479:Neuropeptides / Q000494:pharmacology*; D036361:Peptide Hormones / Q000494:pharmacology; D013270:Stomach / Q000187:drug effects / Q000294:innervation / Q000502:physiology
D005768:Gastrointestinal Hormones; D054439:Ghrelin; D009479:Neuropeptides; C423608:PROK2 protein, human; D036361:Peptide Hormones; C486586:Prok2 protein, mouse; D009037:Motilin; C008680:motilin, Nle(13)-; D008787:Metoclopramide