Cannabinoid receptor-independent inhibition by cannabinoid agonists of the peripheral 5-HT3 receptor-mediated von Bezold-Jarisch reflex.

Abstract

(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.

• Authors: Grzegorz Godlewski, Manfred Göthert, Barbara Malinowska
• Journal: British journal of pharmacology (Br J Pharmacol) Vol. 138 Issue 5 Pg. 767-74 (Mar 2003) ISSN: 0007-1188 [Print] England
• PMID: 12642377 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cannabinoids
• Receptors, Cannabinoid
• Receptors, Drug
• Receptors, Serotonin
• Receptors, Serotonin, 5-HT3
• Serotonin Receptor Agonists

Topics

• Animals
• Cannabinoids (pharmacology)
• Cardiovascular System (drug effects)
• Dose-Response Relationship, Drug
• Male
• Nerve Fibers, Unmyelinated (drug effects, physiology)
• Rats
• Rats, Wistar
• Receptors, Cannabinoid
• Receptors, Drug (agonists, physiology)
• Receptors, Serotonin (physiology)
• Receptors, Serotonin, 5-HT3
• Reflex (drug effects, physiology)
• Serotonin Receptor Agonists (pharmacology)