title: Do cannabinoids exhibit a tyramine-like effect?
abstract: The major constituent of the cannabis plant, Δ(9)-tetrahydrocannabinol, has stimulatory and depressant effects on cardiovascular functions. There is evidence from an in vivo study on the urethane-anaesthetized rat that part of the stimulatory effects is related to a tyramine-like activity. In the present study, we examined whether Δ(9)-tetrahydrocannabinol induces carrier-mediated noradrenaline release in vitro. The study was extended to another phytocannabinoid, cannabidiol, to the synthetic cannabinoids CP 55,940 and WIN 55,212-2 and to the endocannabinoids anandamide and 2-arachidonoyl glycerol. Tissue pieces of the renal cortex from the mouse and the rat were preincubated with (3)H-noradrenaline and superfused. The effect of the cannabinoids on basal (3)H-noradrenaline release was studied. Tyramine served as a positive control. In the mouse kidney, basal (3)H-noradrenaline release was increased by tyramine 0.1, 1 and 10 μM by 39, 91 and 212 %, respectively, and, in the rat kidney, (3)H-noradrenaline release was increased by tyramine 10 μM by 158 %. All effects were abolished by desipramine 1 μM, an inhibitor of the neuronal noradrenaline transporter. The cannabinoids at 0.1, 1 and 10 μM (CP 55,940 at 0.1, 1 and 3.2 μM) did not affect (3)H-noradrenaline release in the mouse kidney. The highest concentration of the cannabinoids (10 μM and in the case of CP 55,940 3.2 μM) also failed to affect (3)H-noradrenaline release in the rat kidney. In conclusion, the cannabinoids Δ(9)-tetrahydrocannabinol, cannabidiol, CP 55,940, WIN 55,212-2, anandamide and 2-arachidonoyl glycerol do not possess a tyramine-like effect on noradrenaline release.
authors.affiliation: Department of Pharmacology and Toxicology, University of Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany.
authors.forename: Eman
authors.initials: E
authors.lastname: Ilayan
authors.forename: Monika
authors.initials: M
authors.lastname: Feliszek
authors.forename: Barbara
authors.initials: B
authors.lastname: Malinowska
authors.forename: Eberhard
authors.initials: E
authors.lastname: Schlicker
mesh_terms: D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology; D048588:Benzoxazines / Q000494:pharmacology; D002185:Cannabidiol / Q000494:pharmacology; D002186:Cannabinoids / Q000494:pharmacology*; D003511:Cyclohexanols / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D013759:Dronabinol / Q000494:pharmacology; D063388:Endocannabinoids / Q000494:pharmacology; D005989:Glycerides / Q000494:pharmacology; D007672:Kidney Cortex / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009025:Morpholines / Q000494:pharmacology; D009281:Naphthalenes / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism*; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D053284:Polyunsaturated Alkamides / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014439:Tyramine / Q000494:pharmacology*
chemical_list: D018759:Adrenergic Uptake Inhibitors; D001095:Arachidonic Acids; D048588:Benzoxazines; D002186:Cannabinoids; D003511:Cyclohexanols; D063388:Endocannabinoids; D005989:Glycerides; D009025:Morpholines; D009281:Naphthalenes; D050484:Norepinephrine Plasma Membrane Transport Proteins; D053284:Polyunsaturated Alkamides; C493228:Slc6a2 protein, mouse; C493226:Slc6a2 protein, rat; D002185:Cannabidiol; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; D013759:Dronabinol; C054649:3-(2-hydroxy-4-(1,1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanol; C094503:glyceryl 2-arachidonate; C078814:anandamide; D009638:Norepinephrine; D014439:Tyramine
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