title: Central and peripheral cannabinoid modulation of gastrointestinal transit in physiological states or during the diarrhoea induced by croton oil.
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.
authors.affiliation: Department of Experimental Pharmacology, University of Naples 'Federico II', via D. Montesano 49, 80131 Naples, Italy. aaizzo@unina.it
authors.forename: A A
authors.initials: AA
authors.lastname: Izzo
authors.forename: L
authors.initials: L
authors.lastname: Pinto
authors.forename: F
authors.initials: F
authors.lastname: Borrelli
authors.forename: R
authors.initials: R
authors.lastname: Capasso
authors.forename: N
authors.initials: N
authors.lastname: Mascolo
authors.forename: F
authors.initials: F
authors.lastname: Capasso
mesh_terms: D000818:Animals; D000930:Antidiarrheals / Q000494:pharmacology / Q000627:therapeutic use; D048588:Benzoxazines; D001892:Camphanes / Q000494:pharmacology / Q000627:therapeutic use; D002186:Cannabinoids / Q000378:metabolism*; D003436:Croton Oil; D003967:Diarrhea / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D005772:Gastrointestinal Transit / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009025:Morpholines / Q000494:pharmacology / Q000627:therapeutic use; D009281:Naphthalenes / Q000494:pharmacology / Q000627:therapeutic use; D010880:Piperidines / Q000494:pharmacology / Q000627:therapeutic use; D011720:Pyrazoles / Q000494:pharmacology / Q000627:therapeutic use; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000819:agonists / Q000037:antagonists & inhibitors; D000077285:Rimonabant
chemical_list: D000930:Antidiarrheals; D048588:Benzoxazines; D001892:Camphanes; D002186:Cannabinoids; D009025:Morpholines; D009281:Naphthalenes; D010880:Piperidines; D011720:Pyrazoles; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; C110630:SR 144528; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; D003436:Croton Oil; D000077285:Rimonabant