Ethanol causes neurogenic vasodilation by TRPV1 activation and CGRP release in the trigeminovascular system of the guinea pig.
Ethanol stimulating transient receptor potential vanilloid 1 (TRPV1) on primary sensory neurons promotes neurogenic inflammation, including calcitonin gene-related peptide (CGRP)-mediated coronary dilation. Alcoholic beverages trigger migraine attacks and activation of trigeminal neurons plays a role in migraine. We have investigated in guinea pigs whether ethanol by TRPV1 stimulation causes neurogenic inflammation in the trigeminovascular system. Ethanol-evoked release of neuropeptides from slices of dura mater was abolished by Ca(2+) removal, capsaicin pretreatment and the TRPV1 antagonist, capsazepine. Intragastric ethanol increased plasma extravasation in dura mater, an effect abolished by capsazepine and the NK1 receptor antagonist, SR140333, and caused vasodilation around the middle meningeal artery, an effect abolished by capsazepine and the CGRP receptor antagonist, BIBN4096BS. Vasodilation of meningeal vessels by TRPV1 activation and CGRP release may be relevant to the mechanism by which alcohol ingestion triggers migraine attacks.
Nicoletti
P
P
Clinical Pharmacology Unit, Department of Critical Care Medicine and Surgery, University of Florence, Florence, Italy.
Trevisani
M
M
Manconi
M
M
Gatti
R
R
De Siena
G
G
Zagli
G
G
Benemei
S
S
Capone
J A
JA
Geppetti
P
P
Pini
L A
LA
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism*; D004388:Dura Mater / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism; D000431:Ethanol / Q000494:pharmacology*; D006168:Guinea Pigs; D008297:Male; D050916:TRPV Cation Channels / Q000378:metabolism* / Q000502:physiology; D012668:Trigeminal Ganglion / Q000098:blood supply* / Q000187:drug effects* / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology
D050916:TRPV Cation Channels; C494482:TRPV1 protein, human; D014665:Vasodilator Agents; D000431:Ethanol; D015740:Calcitonin Gene-Related Peptide