Cannabinoid inhibition of capsaicin-sensitive sensory neurotransmission in the rat mesenteric arterial bed.
The present study investigated whether cannabinoids can modulate neurotransmission mediated by capsaicin-sensitive sensory nerves in the rat isolated mesenteric arterial bed. Sensory neurogenic vasorelaxation mediated by electrical field stimulation was concentration-dependently attenuated by HU210 (0.1-3 microM), a cannabinoid receptor agonist (from 62+/-8.3% to 6+/-2.1% at 3 microM HU210). HU210 had no effect on relaxation to exogenous calcitonin gene-related peptide, indicating a prejunctional action. The action of HU210 (1 microM) was not affected by LY320135 (1 microM) or SR144528 (1 microM), cannabinoid CB(1) and CB(2) receptor antagonists, respectively. SR141716A (0.01-1 microM), a cannabinoid CB(1) receptor antagonist, concentration-dependently augmented vasorelaxation to electrical field stimulation, but had no effect on responses to calcitonin gene-related peptide and capsaicin, indicating a possible role of endogenous cannabinoids in sensory neurotransmission in rat mesenteric arteries. These data show that the cannabinoid receptor agonist HU210 inhibits prejunctionally sensory neurotransmission in rat mesenteric arteries and that this action is independent of cannabinoid CB(1)- or CB(2)-like receptors.
Ralevic
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School of Biomedical Sciences, University of Nottingham Medical School, Queen's Medical Centre, NG7 2UH, Nottingham, UK. vera.ralevic@nottingham.ac.uk
Kendall
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DA
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D001572:Benzofurans / Q000494:pharmacology; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D001892:Camphanes / Q000494:pharmacology; D002186:Cannabinoids / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002211:Capsaicin / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D013759:Dronabinol / Q000031:analogs & derivatives* / Q000494:pharmacology; D004558:Electric Stimulation; D004594:Electrophysiology; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000294:innervation*; D009475:Neurons, Afferent / Q000187:drug effects* / Q000502:physiology; D009599:Nitroprusside / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D043885:Receptor, Cannabinoid, CB2; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000037:antagonists & inhibitors / Q000378:metabolism; D000077285:Rimonabant; D009435:Synaptic Transmission / Q000187:drug effects*; D013997:Time Factors; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
D001572:Benzofurans; D001892:Camphanes; D002186:Cannabinoids; C469526:Cnr2 protein, rat; D010880:Piperidines; D011720:Pyrazoles; D043885:Receptor, Cannabinoid, CB2; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; C110630:SR 144528; D014665:Vasodilator Agents; D009599:Nitroprusside; D000244:Adenosine Diphosphate; D013759:Dronabinol; C110158:LY 320135; D015740:Calcitonin Gene-Related Peptide; C062018:HU 211; D000077285:Rimonabant; D002211:Capsaicin