Centrally administered bombesin affects gastrointestinal transit and colonic bead expulsion through supraspinal mechanisms

RJ Koslo, TF Burks and F Porreca

Effects of bombesin on gastrointestinal transit and colonic bead expulsion (CBE) were studied in male, ICR mice. Mice received graded doses of bombesin or saline by either the i.c.v., intrathecal (i.t.) or i.p. routes; morphine was studied as the reference compound. Both compounds slowed gastrointestinal transit in a dose-dependent manner by these routes. Intracerebroventricular bombesin was 13.5 and 3406 times more potent than the i.t. and i.p. peptide, respectively. Intracerebroventricular or i.t. bombesin or morphine also produced dose- related inhibition of CBE. Intracerebroventricular bombesin was 1.54 times more potent than i.t. bombesin, whereas i.p. bombesin at doses 11,000 times greater (10 micrograms/kg; 25-g mouse) had no effect on CBE. Gastrointestinal transit and CBE were also studied in spinally transected (second thoracic vertebra) mice in which brain-spinal cord communication (neural and cerebrospinal fluid) had been interrupted. Cord transection eliminated the inhibition of gastrointestinal transit by i.t., but not i.c.v., bombesin. In contrast, morphine was effective by either route in normal or spinally transected mice. The CBE effects of i.t., but not i.c.v., bombesin were eliminated by spinal transection, whereas morphine was still effective by either the i.c.v. or i.t. route. These results suggest that 1) centrally administered bombesin acts at a central site to produce inhibition of gastrointestinal transit and CBE, 2) morphine inhibits gastrointestinal transit and CBE at both spinal or supraspinal sites, independent of an intact brain-cord axis and 3) i.t., but not i.c.v., bombesin requires communication between these two central sites. Intrathecal bombesin requires activation of supraspinal sites to produce its gut effects.

Volume 238, Issue 1, pp. 62-67, 07/01/1986
Copyright © 1986 by American Society for Pharmacology and Experimental Therapeutics