Centrally-mediated bombesin effects on gastrointestinal motility.
Administration of bombesin into the lateral cerebral ventricle (i.c.v.) of rats results in a dose-related delay in gastric emptying and small intestinal transit. Recordings of intestinal intraluminal pressure in this species show that the i.c.v. peptide produces a dose-related increase in the frequency of duodenal contractions, and a complex inhibitory/excitatory jejunal effect at low and high doses, respectively. Intrathecal (i.th.) or i.c., but not intraperitoneal (i.p.), bombesin produces a dose-related slowing of gastrointestinal and colonic transit in mice. I.c.v. bombesin is 13.5 and 3406 times more potent in inhibition of gastrointestinal transit than when given by the i.th. or i.p. routes, respectively. Similarly, the i.c.v. peptide is 1.54 and over 11000 times more potent in slowing mouse colonic transit than when given by the i.th. or i.p. routes, respectively. The substance P analogue, D-Arg1, D-Pro2, D-Trp7,9, Leu11-Substance P (DAPTL-SP)(a reported bombesin antagonist in vitro) was not effective in blocking the gastrointestinal transit effects of the peptide in vivo. Transection of the spinal cord at the level of the second thoracic vertebra (T2) eliminates the gastrointestinal and colonic effects of i.th., but not i.c.v. bombesin. Thus, bombesin can affect motor function of the gut via activity within the brain or spinal cord of rats and mice; the activity of the peptide when given at the supraspinal level depends on an intact vagus nerve and adrenal-pituitary axis, while the activity of the peptide given at the spinal level appears to depend on the integrity of ascending spinal-supraspinal pathways.
Porreca
F
F
Burks
T F
TF
Koslo
R J
RJ
D000818:Animals; D001839:Bombesin / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D001933:Brain Stem / Q000187:drug effects / Q000502:physiology; D002490:Central Nervous System / Q000187:drug effects* / Q000502:physiology; D005260:Female; D005769:Gastrointestinal Motility / Q000187:drug effects*; D007274:Injections, Intraperitoneal; D007276:Injections, Intraventricular; D007278:Injections, Spinal; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013045:Species Specificity; D013116:Spinal Cord / Q000502:physiology; D013373:Substance P / Q000031:analogs & derivatives / Q000494:pharmacology; D014630:Vagus Nerve / Q000502:physiology
D010455:Peptides; D013373:Substance P; C038073:substance P, Arg(1)-Pro(2)-Trp(7),(9)-LeuNH(2)(11)-; D001839:Bombesin