Studies on the structure-activity of motilin in vivo. Effect of motilin synthetic analogues in conscious dog.
Synthetic analogues of motilin were tested for their capacity to stimulate the intestinal motor activity of the conscious dog. Physiological doses (75 pmol/kg) of motilin 1-22 and of motilin fragments 1-21, 1-20 and 1-19 induced premature periods of phase III activity in all tested animals. Motilin fragments 1-15, 1-12, 1-11 and 1-10 failed to influence the intestinal myoelectrical activity even when given at doses 10-times superior (750 pmol/kg). Motilin-like-immunoreactivity was measured in plasma during the analogues infusion. During the infusion of the bioactive analogues (1-22, 1-21, 1-20, 1-19), plasma motilin increased by 174 +/- 25 fmol/ml while a small rise (22 +/- 7.6 fmol) was noted with the inactive fragments (P < 0.001). Our data are in agreement with the in vitro findings that the N-terminal portion of the motilin molecule is responsible for its biological activity and suggests that the middle portion of the molecule is important to prevent degradation and maintain biological activity in vivo.
Raymond
M C
MC
Centre de Recherche Clinique André-Viallet, Hôpital St.-Luc, Université de Montréal, Québec, Canada.
Boivin
M
M
St-Pierre
S
S
Gagnon
D
D
Poitras
P
P
D000818:Animals; D001682:Biological Availability; D004285:Dogs; D005260:Female; D005769:Gastrointestinal Motility / Q000187:drug effects*; D009037:Motilin / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D010446:Peptide Fragments / Q000494:pharmacology; D011863:Radioimmunoassay; D013329:Structure-Activity Relationship
D010446:Peptide Fragments; D009037:Motilin