Delta 9-tetrahydrocannabinol inhibits electrically-evoked CGRP release and capsaicin-sensitive sensory neurogenic vasodilatation in the rat mesenteric arterial bed.
OBJECTIVE
Calcitonin gene-related peptide (CGRP) is a sensory neurotransmitter in the rat mesenteric arterial bed. Certain cannabinoids can inhibit, via CB(1) receptors, vasorelaxant responses to electrical field stimulation (EFS) of sensory nerves in the rat mesentery, but the mechanism of the inhibitory effect of the cannabinoid delta 9-tetrahydrocannabinol (THC) is unclear. This study assessed directly the effect of THC on EFS-induced release of CGRP from sensory nerves in the rat mesenteric bed and investigated the possible involvement of cannabinoid receptors and transient receptor potential (TRP) ion channels.


METHODS
Rat mesenteric beds were perfused with physiological salt solution. Sensory nerves were stimulated electrically and perfusate levels of CGRP measured by immunoassay. The effects of THC on EFS-induced CGRP release and vasorelaxant responses to sensory nerve stimulation were investigated in the absence and presence of cannabinoid antagonists and TRP channel blockers.


RESULTS
EFS evoked a release of CGRP and vasodilatation of the mesenteric beds. THC inhibited the electrically-evoked release of CGRP and sensory neurogenic vasorelaxation. The effect of THC was unaffected by the CB1 antagonist AM251, the CB2 antagonist AM630 or the TRPV1 receptor antagonist capsazepine, but was blocked by the TRP channel blocker ruthenium red.


CONCLUSIONS
THC inhibits the EFS-induced release of CGRP (and subsequent vasorelaxation), from capsaicin-sensitive sensory nerves in the rat perfused mesentery. The effect of THC was not mediated by CB1, CB2 or TRPV1 receptors, but was sensitive to ruthenium red, suggesting a possible involvement of TRP ion channels.
Wilkinson
J D
JD
Centre for Integrated Systems Biology & Medicine, School of Biomedical Sciences, University of Nottingham, Nottingham, UK.
Kendall
D A
DA
Ralevic
V
V
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism*; D002211:Capsaicin / Q000031:analogs & derivatives / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D013759:Dronabinol / Q000494:pharmacology*; D004558:Electric Stimulation; D007211:Indoles / Q000494:pharmacology; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D008729:Methoxamine / Q000494:pharmacology; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors; D012430:Ruthenium Red / Q000494:pharmacology; D013997:Time Factors; D014664:Vasodilation / Q000187:drug effects*