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Cannabidiol lacks the vanilloid VR1-mediated vasorespiratory effects of capsaicin and anandamide in anaesthetised rats
- Source :
- European journal of pharmacology. 491(2-3)
- Publication Year :
- 2004
-
Abstract
- The results of vasorespiratory studies in rats anaesthetised with pentobarbital show that (+/-) cannabidiol, a cannabinoid that lacks psychotropic actions and is inactive at cannabinoid (CB) receptors, does not affect respiration or blood pressure when injected (1-2000 microg; 3.2-6360 nmol i.a.). Cannabidiol in doses up to 2 mg (6360 nmol) i.a. or i.v. did not affect the fall in mean blood pressure or the increase in ventilation (respiratory minute volume) caused by capsaicin and high doses of anandamide, responses that are mediated by activation of vanilloid VR1 (TRPV1) receptors in this species. Similar results were obtained with (-) cannabidiol (30-100 microg i.a.; 95-318 nmol). It has previously been shown using human embryonic kidney (HEK) cells over-expressing vanilloid human VR1 (hVR1) receptors that cannabidiol is a full agonist at vanilloid VR1 receptors in vitro. However, in the intact rat cannabidiol lacked vanilloid VR1 receptor agonist effects. We conclude that there are substantial functional differences between human and rat vanilloid VR1 receptors with respect to the actions of cannabidiol as an agonist at vanilloid VR1 receptors. Studies in vivo show that cannabidiol lacks any significant effect on mean blood pressure or respiratory minute volume when injected i.a. or i.v., and that this cannabinoid does not modulate the vanilloid VR1 receptor-mediated cardiovascular and ventilatory changes reflexly evoked by capsaicin or anandamide in rats anaesthetised with pentobarbital.
- Subjects :
- Agonist
Male
medicine.drug_class
Polyunsaturated Alkamides
medicine.medical_treatment
Receptors, Drug
TRPV1
Blood Pressure
Arachidonic Acids
Pharmacology
chemistry.chemical_compound
medicine
Animals
Cannabidiol
Hyperventilation
Anesthesia
Rats, Wistar
Receptor
Dose-Response Relationship, Drug
Anandamide
Endocannabinoid system
Rats
chemistry
Capsaicin
lipids (amino acids, peptides, and proteins)
Cannabinoid
Hypotension
Pulmonary Ventilation
medicine.drug
Endocannabinoids
Subjects
Details
- ISSN :
- 00142999
- Volume :
- 491
- Issue :
- 2-3
- Database :
- OpenAIRE
- Journal :
- European journal of pharmacology
- Accession number :
- edsair.doi.dedup.....a2e9ae618bbd9ce0568d20c693fab99a