Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P21554 (cannabinoid receptor)
 3,582 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In anaesthetized rats activation of vanilloid receptors on sensory vagal nerves elicits rapid bradycardia and hypotension (Bezold-Jarisch reflex). Recent in vitro experiments revealed that the endogenous cannabinoid ligand anandamide acts as an agonist at the vanilloid VRI receptors. The present study was aimed at examining whether vanilloid VR1 receptors are involved in the cardiovascular effects of anandamide in the anaesthetized rat. Intravenous injection of anandamide, its stable analogue methanandamide and the vanilloid receptor agonist capsaicin produced a dose-dependent immediate and short-lasting decrease in heart rate and blood pressure with the following rank order of potencies: capsaicin > methanandamide > anandamide. This bradycardia was dose-dependently diminished by the selective vanilloid receptor antagonist capsazepine (0.3-3 micromol/kg) and the nonselective inhibitor of these receptors, ruthenium red (1-10 micromol/kg). Both antagonists reduced or tended to reduce the hypotension stimulated by the agonists. Following this bradycardia and hypotension (presumably evoked by the Bezold-Jarisch reflex; phase I), capsaicin, anandamide and methanandamide led to a brief vasopressor effect (phase II). Subsequently both anandamides, but not capsaicin, induced a more prolonged decrease in blood pressure (phase III). Capsazepine and ruthenium red (at doses up to 3 tmol/kg and 10 micromol/kg, respectively) failed to affect these changes in blood pressure. The cannabinoid CB1 receptor antagonist SR 141716 at 3 micromol/kg abolished the prolonged decrease in blood pressure (phase III) induced by anandamide and methanandamide, but had no effect on the reflex bradycardia and hypotension (phase I) and on the subsequent vasopressor effect (phase II) evoked by capsaicin, anandamide and methanandamide. In conclusion, the endogenous cannabinoid receptor agonist anandamide and its stable analogue methanandamide induce reflex bradycardia and hypotension (phase I) by activating the vanilloid VRI receptor. Whereas the mechanism underlying the brief vasopressor effect (phase II) is unknown, the prolonged hypotension (phase III) results from stimulation of the cannabinoid CB1 receptor.
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PMID:Anandamide and methanandamide induce both vanilloid VR1- and cannabinoid CB1 receptor-mediated changes in heart rate and blood pressure in anaesthetized rats. 1177 12

(1) On the basis of previous findings that cannabinoids inhibit the function of human and rat 5-HT(3) receptors in vitro, we investigated whether cannabinoid receptor agonists also modulate the activity of the rat peripheral 5-HT(3) receptors on the terminals of cardiopulmonary afferent C-fibres in vivo. (2) In urethane-anaesthetized rats, pre-treated intravenously (i.v.) with the CB(1) receptor antagonist SR 141716A (3 micro mol kg(-1)) and with the beta(1)/beta(2) adrenoceptor antagonist propranolol (0.3-0.4 micro mol kg(-1)), bolus injection of the serotonin 5-HT(3) receptor agonist phenylbiguanide (3-10 micro g kg(-1), i.v.) or the vanilloid VR1 receptor agonist capsaicin (3-10 micro g kg(-1), i.v.) caused an immediate decrease in heart rate and mean arterial blood pressure (the von Bezold-Jarisch reflex). (3) The phenylbiguanide-induced bradycardia was dose-dependently attenuated by the cannabinoid receptor agonists CP 55,940 (0.1-1 micro mol kg(-1), i.v.) and WIN 55,212-2 (0.1-3 micro mol kg(-1), i.v.) 20 min after injection, but not by the inactive S-(-)enantiomer of the latter, WIN 55,212-3 (1 micro mol kg(-1), i.v.). The inhibition was reversible within 30 min. The extent of inhibition by the highest doses of cannabinoid receptor agonists amounted to about 50%. Both cannabinoid receptor agonists failed to affect the capsaicin-evoked bradycardia. (4) In conclusion, our results demonstrate that cannabinoid receptor agonists modulate the von Bezold-Jarisch reflex by inhibiting peripheral serotonin 5-HT(3) receptors in rats in vivo. An analogous mechanism of cannabinoid receptor agonists may be assumed to be involved in other serotonin 5-HT(3) receptor-mediated responses.
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PMID:Cannabinoid receptor-independent inhibition by cannabinoid agonists of the peripheral 5-HT3 receptor-mediated von Bezold-Jarisch reflex. 1264 77