Central and peripheral cannabinoid modulation of gastrointestinal transit in physiological states or during the diarrhoea induced by croton oil

Br J Pharmacol. 2000 Apr;129(8):1627-32. doi: 10.1038/sj.bjp.0703265.

Abstract

We have evaluated the effect of cannabinoid drugs, administered intraperitoneally (i.p.) or intracerebroventricularly (i.c.v.) on upper gastrointestinal transit in control and in croton oil-treated mice. The cannabinoid agonists, WIN 55,212-2 (2-239 nmol mouse(-1)) and cannabinol (24-4027 nmol mouse(-1)), decreased while the CB(1) antagonist SR141716A (2-539 nmol mouse(-1)) increased transit in control mice. WIN 55,212-2, cannabinol and SR141716A had lower ED(50) values when administered i.c.v., than when administered i.p. The CB(2) antagonist SR144528 (52 nmol mouse(-1), i.p.) was without effect. During croton oil (0.01 ml mouse(-1), p.o.)-induced diarrhoea, the ED(50) values of i.p. -injected WIN 55,212-2 and cannabinol (but not SR141716A) were significantly decreased (compared to control mice). However, the ED(50) values of WIN 55,212-2 were similar after i.p. or i.c.v. administration. The inhibitory effects of WIN 55,212-2 and cannabinol were counteracted by SR141716A (16 nmol mouse(-1), i.p.) but not by SR144528 (52 nmol mouse(-1), i.p.) both in control and croton-oil treated mice. Ganglionic blockade with hexamethonium (69 nmol mouse(-1), i.p.) did not modify the inhibitory effect of i.p. -injected cannabinoid agonists either in control or in croton-oil treated mice. The lower ED(50) values of cannabinoid drugs after i.c.v. administration suggest a central (CB(1)) site of action. However, a peripheral site of action is suggested by the lack of effect of hexamethonium. In addition, croton oil-induced diarrhoea enhances the effect of cannabinoid agonists by a peripheral mechanism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antidiarrheals / pharmacology
  • Antidiarrheals / therapeutic use
  • Benzoxazines
  • Camphanes / pharmacology
  • Camphanes / therapeutic use
  • Cannabinoids / metabolism*
  • Croton Oil
  • Diarrhea / chemically induced
  • Diarrhea / drug therapy
  • Diarrhea / metabolism
  • Diarrhea / physiopathology*
  • Gastrointestinal Transit / drug effects
  • Gastrointestinal Transit / physiology*
  • Male
  • Mice
  • Mice, Inbred ICR
  • Morpholines / pharmacology
  • Morpholines / therapeutic use
  • Naphthalenes / pharmacology
  • Naphthalenes / therapeutic use
  • Piperidines / pharmacology
  • Piperidines / therapeutic use
  • Pyrazoles / pharmacology
  • Pyrazoles / therapeutic use
  • Receptors, Cannabinoid
  • Receptors, Drug / agonists
  • Receptors, Drug / antagonists & inhibitors
  • Rimonabant

Substances

  • Antidiarrheals
  • Benzoxazines
  • Camphanes
  • Cannabinoids
  • Morpholines
  • Naphthalenes
  • Piperidines
  • Pyrazoles
  • Receptors, Cannabinoid
  • Receptors, Drug
  • SR 144528
  • Win 55212-2
  • Croton Oil
  • Rimonabant