title: Differential distribution of functional cannabinoid CB1 receptors in the mouse gastroenteric tract.
abstract: Recently, the gastrointestinal pharmacology of cannabinoid CB(1) receptors has been extensively explored. We employed western blotting and immunohistochemistry techniques to study the distribution of the cannabinoid CB(1) receptor protein in the mouse gastroenteric tract. The cannabinoid CB(1) receptor peptide was detected by western blotting only in its glycosylated form (63 kDa) with a significant differential distribution. The highest levels of expression were detected in the stomach and in the colon, while the pyloric valve was devoid of any cannabinoid CB(1) receptor protein. The immunohistochemical study showed intense cannabinoid CB(1) receptor immunoreactivity in ganglia subadjacent to the gastric epithelium and in the smooth muscle layers of both the small and large intestine. Only the small intestine showed (-)-3-[2-hydroxyl-4-(1,1-dimethylheptyl)-phenyl]-4-(3-hydroxylpropyl) cyclohexan-1-ol) ([3H]CP 55,940) specific binding (27%). These receptors mediated pharmacologically significant effects since the cannabinoid CB(1) receptor agonist R(-)-7-hydroxy-delta-6-tetra-hydrocannabinol-dimethylheptyl (HU 210) dose dependently inhibited gastrointestinal transit up to 70%, while the cannabinoid CB(1) receptor antagonist N-piperidino-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methylpyrazole-3-carboxamide (SR 141716A) increased gastrointestinal transit. Moreover, the dose of 0.3 microg/kg of HU 210, devoid per se of any activity on mouse intestinal propulsion, blocked the increased gastroenteric transit induced by the cannabinoid CB(1) antagonist SR 141716A.
authors.affiliation: Neuroscienze Scarl, via Palabanda, 9 09124-I, Cagliari, Italy.
authors.forename: Maria Antonietta
authors.initials: MA
authors.lastname: Casu
authors.forename: Anna
authors.initials: A
authors.lastname: Porcella
authors.forename: Stefania
authors.initials: S
authors.lastname: Ruiu
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Saba
authors.forename: Giorgio
authors.initials: G
authors.lastname: Marchese
authors.forename: Mauro Antonio Maria
authors.initials: MA
authors.lastname: Carai
authors.forename: Roberta
authors.initials: R
authors.lastname: Reali
authors.forename: Gian Luigi
authors.initials: GL
authors.lastname: Gessa
authors.forename: Luca
authors.initials: L
authors.lastname: Pani
mesh_terms: D000818:Animals; D000932:Antiemetics / Q000494:pharmacology; D001667:Binding, Competitive; D015153:Blotting, Western; D003511:Cyclohexanols / Q000378:metabolism; D004064:Digestive System / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D013759:Dronabinol / Q000031:analogs & derivatives* / Q000494:pharmacology; D005753:Gastric Mucosa / Q000378:metabolism; D005772:Gastrointestinal Transit / Q000187:drug effects; D007150:Immunohistochemistry; D007420:Intestine, Large / Q000737:chemistry / Q000378:metabolism; D007421:Intestine, Small / Q000737:chemistry / Q000378:metabolism; D008297:Male; D051379:Mice; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000032:analysis / Q000037:antagonists & inhibitors / Q000502:physiology*; D000077285:Rimonabant; D013270:Stomach / Q000737:chemistry; D014316:Tritium
chemical_list: D000932:Antiemetics; D003511:Cyclohexanols; D010880:Piperidines; D011720:Pyrazoles; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; D014316:Tritium; D013759:Dronabinol; C054649:3-(2-hydroxy-4-(1,1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanol; C062018:HU 211; D000077285:Rimonabant