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

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 rat 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• 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•-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 into 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.

Current Knowledge on the Vascular Effects of Menthol

“…Furthermore, acetate, a metabolite of aldehyde also displays a moderate vasodilator response (Altura and Altura, 1982). In contrast, some vascular beds tend to be constricted by ethanol, such as the cerebral Altura, 1982, 1987), coronary (Altura et al, 1983), mesenteric (Toda et al, 1983;Ru et al, 2008), aortic (Ru et al, 2008), an effect that may involve extra-endothelial TRPV1 channels (Cleland et al, 2019). Ethanol could interfere with the vascular action of menthol via direct and/or indirect mechanisms both in vitro and in vivo.…”

TRPV1 Channel Contributes to the Behavioral Hypersensitivity in a Rat Model of Complex Regional Pain Syndrome Type 1

“…The primary antibodies used were rabbit anti-TRPV1 (ab6166, Abcam), mouse anti-GFAP (Abcam), mouse anti-OX42 (Abcam), rabbit anti-NeuN (Abcam). The specificity of the TRPV1 antibody has been validated using TRPV1 knockout mice in a previous study (North et al, 2018). The following day, the sections were rinsed with TBST (6 × 10 min) and incubated for 1 h with a mixture of corresponding secondary antibodies.…”

Large conductance voltage- and calcium-gated potassium channels (BK) in cerebral artery myocytes of perinatal fetal primates share several major characteristics with the adult phenotype

“…Baboon fetal and maternal cerebral artery segments were dissected out and subjected to surface protein biotinylation using the Pierce ™ Cell Surface Protein Isolation Kit (Thermo Fisher Scientific, Waltham, MA), following manufacturer’s instructions. Surface (extracellular) versus intracellular protein was analyzed by Western blotting using standard methodology as described [ 22 ]. The presence of a single band in both protein fractions was detected following staining with mouse monoclonal anti- KCNMA1 antibody (1:1,000 dilution; clone L6/60, UC Davis/NIH NeuroMab Facility).…”