Extra-endothelial TRPV1 channels participate in alcohol and caffeine actions on cerebral artery diameter

Kelsey C. North, Jennifer Chang, Anna Bukiya, Alejandro Dopico

Research output: Contribution to journalArticle

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Abstract

Alcohol (ethyl alcohol; ethanol) and caffeine are the two most widely used psychoactive substances in the world. Caffeine and ethanol have both been reported to constrict cerebral arteries in several species, including humans. We have recently shown that application of 10-μM caffeine mixed with 50 mM ethanol to in vitro pressurized cerebral arteries of rats reduced ethanol-induced constriction. This effect was dependent on the presence of nitric oxide (NO) and could be observed in de-endothelialized arteries supplied with the NO[rad] donor sodium nitroprusside (SNP). The molecular target(s) of ethanol-caffeine interaction in cerebral arteries has remained unknown. In the present work, we used rat and mouse middle cerebral arteries (MCA) to identify the extra-endothelial effectors of NO[rad]-mediated, caffeine-induced protection against ethanol-evoked arterial constriction. Constriction of intact MCA of rat by either 50 mM ethanol or 10 μM caffeine was ablated in the presence of a selective TRPV1 pharmacological blocker. TRPV1 pharmacological block, but not block of TRPA1, PKG, or BK channels, removed caffeine-induced protection against ethanol-evoked rat MCA constriction, whether evaluated in arteries with intact endothelium or in SNP-supplemented, de-endothelialized arteries. In mouse arteries, caffeine-induced protection against ethanol-induced MCA constriction was significantly amplified, resulting in actual vasodilation, upon pharmacological block of TRPV1, and in TRPV1 knock-out arteries. Despite some species-specific differences, our study unequivocally demonstrates the presence of functional, extra-endothelial TRPV1 that participates in both endothelium-independent MCA constriction by separate exposure to ethanol or caffeine and caffeine-induced protection against ethanol-evoked MCA constriction.

Original languageEnglish (US)
Pages (from-to)45-55
Number of pages11
JournalAlcohol
Volume73
DOIs
StatePublished - Dec 1 2018

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Cerebral Arteries
Caffeine
Ethanol
alcohol
Alcohols
Constriction
Middle Cerebral Artery
Arteries
Rats
interaction
Nitric Oxide
Nitroprusside
Pharmacology
Endothelium
Large-Conductance Calcium-Activated Potassium Channels
Nitric Oxide Donors
Vasodilation

All Science Journal Classification (ASJC) codes

  • Health(social science)
  • Biochemistry
  • Toxicology
  • Neurology
  • Behavioral Neuroscience

Cite this

Extra-endothelial TRPV1 channels participate in alcohol and caffeine actions on cerebral artery diameter. / North, Kelsey C.; Chang, Jennifer; Bukiya, Anna; Dopico, Alejandro.

In: Alcohol, Vol. 73, 01.12.2018, p. 45-55.

Research output: Contribution to journalArticle

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