Regulation of transient receptor potential channels of melastatin type 8 (TRPM8): Effect of cAMP, cannabinoid CB1 receptors and endovanilloids

Petrocellis, Luciano De; Starowicz, Katarzyna; Moriello, Aniello Schiano; Vivese, Marta; Orlando, Pierangelo; Marzo, Vincenzo Di

doi:10.1016/j.yexcr.2007.01.008

Cited by 135 publications

(125 citation statements)

References 44 publications

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“…Many recent studies (6,8,34,36) have implicated the TRPM8 channel as a regulator of intracellular calcium. Increased intracellular Ca 2ϩ concentrations associated with channel activation (38) would be expected to cause contraction.…”

Section: Discussionmentioning

confidence: 99%

Transient receptor potential melastatin 8 channel involvement in the regulation of vascular tone

Johnson¹,

Melanaphy²,

Purse³

et al. 2009

American Journal of Physiology-Heart and Circulatory Physiology

133

137

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Johnson CD, Melanaphy D, Purse A, Stokesberry SA, Dickson P, Zholos AV. Transient receptor potential melastatin 8 channel involvement in the regulation of vascular tone. Am J Physiol Heart Circ Physiol 296: H1868 -H1877, 2009. First published April 10, 2009 doi:10.1152/ajpheart.01112.2008.-The transient receptor potential melastatin 8 (TRPM8) channel has been characterized as a cold and menthol receptor expressed in a subpopulation of sensory neurons but was recently identified in other tissues, including the respiratory tract, urinary system, and vasculature. Thus TRPM8 may play multiple functional roles, likely to be in a tissue-and activation statedependent manner. We examined the TRPM8 channel presence in large arteries from rats and the functional consequences of their activation. We also aimed to examine whether these channels contribute to control of conscious human skin blood flow. TRPM8 mRNA and protein were detected in rat tail, femoral and mesenteric arteries, and thoracic aorta. This was confirmed in single isolated vascular myocytes by immunocytochemistry. Isometric contraction studies on endothelium-denuded relaxed rat vessels found small contractions on application of the TRPM8-specific agonist menthol (300 M). However, both menthol and another agonist icilin (50 M) caused relaxation of vessels precontracted with KCl (60 mM) or the ␣-adrenoceptor agonist phenylephrine (2 M) and a reduction in sympathetic nerve-mediated contraction. These effects were antagonized by bromoenol lactone treatment, suggesting the involvement of Ca 2ϩ -independent phospholipase A 2 activation in TRPM8-mediated vasodilatation. In thoracic aorta with intact endothelium, menthol-induced inhibition of KCl-induced contraction was enhanced. This was unaltered by preincubation with either N -nitro-L-arginine methyl ester (L-NAME; 100 nM), a nitric oxide synthase inhibitor, or the ACh receptor antagonist atropine (1 M). Application of menthol (3% solution, topical application) to skin caused increased blood flow in conscious humans, as measured by laser Doppler fluximetry. Vasodilatation was markedly reduced or abolished by prior application of L-NAME (passive application, 10 mM) or atropine (iontophoretic application, 100 nM, 30 s at 70 A). We conclude that TRPM8 channels are present in rat artery vascular smooth muscle and on activation cause vasoconstriction or vasodilatation, dependent on previous vasomotor tone. TRPM8 channels may also contribute to human cutaneous vasculature control, likely with the involvement of additional neuronal mechanisms.human; rat; artery ION CHANNELS, ESPECIALLY Ca 2ϩ -permeable channels, are of central importance to the control of vascular tone as well as long-term phenotypic remodeling. In recent years, members of the transient receptor potential (TRP) superfamily of cation channels attracted considerable interest as novel nonvoltage gated Ca 2ϩ permeable cation channels, important determinants of vascular function and disease (2, 4, 5, 13). These channels can be constitutively active or acti...

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Section: Discussionmentioning

confidence: 99%

Transient receptor potential melastatin 8 channel involvement in the regulation of vascular tone

Johnson¹,

Melanaphy²,

Purse³

et al. 2009

American Journal of Physiology-Heart and Circulatory Physiology

133

137

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“…In addition to CB1, AEA can interact with various transient TRP channels involved in nociception, including TRPV1 (8), TRPA1 (192), and TRPM8 (195). Nevertheless, studies using CB1 and CB2 knockout mice have suggested that endocannabinoids produce analgesia mostly via cannabinoid receptor-mediated mechanisms (433).…”

Section: Painmentioning

confidence: 99%

From Phytocannabinoids to Cannabinoid Receptors and Endocannabinoids: Pleiotropic Physiological and Pathological Roles Through Complex Pharmacology

Ligresti¹,

Petrocellis²,

Marzo³

2016

Physiological Reviews

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341

318

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Apart from having been used and misused for at least four millennia for, among others, recreational and medicinal purposes, the cannabis plant and its most peculiar chemical components, the plant cannabinoids (phytocannabinoids), have the merit to have led humanity to discover one of the most intriguing and pleiotropic endogenous signaling systems, the endocannabinoid system (ECS). This review article aims to describe and critically discuss, in the most comprehensive possible manner, the multifaceted aspects of 1) the pharmacology and potential impact on mammalian physiology of all major phytocannabinoids, and not only of the most famous one ⌬ 9 -tetrahydrocannabinol, and 2) the adaptive prohomeostatic physiological, or maladaptive pathological, roles of the ECS in mammalian cells, tissues, and organs. In doing so, we have respected the chronological order of the milestones of the millennial route from medicinal/recreational cannabis to the ECS and beyond, as it is now clear that some of the early steps in this long path, which were originally neglected, are becoming important again. The emerging picture is rather complex, but still supports the belief that more important discoveries on human physiology, and new therapies, might come in the future from new knowledge in this field.

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“…Immediately thereafter, anandamide was shown to be the first endogenous agonist of both human and rat TRPV1 channels [6], although it was soon clear that this endocannabinoid was not the only lipid mediator capable of exerting this function [7]. Anandamide was later found also to antagonize TRP channels of melastatin type-8 (TRPM8), which are instead activated by low temperatures and menthol [8], whereas the other cold-activated TRP, the TRP channel of ankyrin type-1 (TRPA1), activated by mustard oils, was sensitive only to high micromolar concentrations of the endocannabinoid. The stimulatory, and subsequently desensitizing, effects of anandamide at TRPV1 have been reported in hundreds of studies and represent one of the most important mechanisms, after CB1 activation, through which this lipid mediator exerts its biological functions [9].…”

Section: Endocannabinoids Plant Cannabinoids and Thermo-trpsmentioning

confidence: 99%

The Endocannabinoid System and its Modulation by Phytocannabinoids

2015

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The endocannabinoid system is currently defined as the ensemble of the two 7-transmembrane-domain and G protein-coupled receptors for Δ 9 -tetrahydrocannabinol (but not for most other plant cannabinoids or phytocannabinoids)-cannabinoid receptor type-1 (CB 1 R) and cannabinoid receptor type-2 (CB 2 R); their two most studied endogenous ligands, the "endocannabinoids" N-arachidonoylethanolamine (anandamide) and 2-arachidonoylglycerol (2-AG); and the enzymes responsible for endocannabinoid metabolism. However, anandamide and 2-AG, and also the phytocannabinoids, have more molecular targets than just CB 1 R and CB 2 R. Furthermore, the endocannabinoids, like most other lipid mediators, have more than just one set of biosynthetic and degrading pathways and enzymes, which they often share with "endocannabinoid-like" mediators that may or may not interact with the same proteins as Δ 9 -tetrahydrocannabinol and other phytocannabinoids. In some cases, these degrading pathways and enzymes lead to molecules that are not inactive and instead interact with other receptors. Finally, some of the metabolic enzymes may also participate in the chemical modification of molecules that have very little to do with endocannabinoid and cannabinoid targets. Here, we review the whole world of ligands, receptors, and enzymes, a true "endocannabinoidome", discovered after the cloning of CB 1 R and CB 2 R and the identification of anandamide and 2-AG, and its interactions with phytocannabinoids.

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Regulation of transient receptor potential channels of melastatin type 8 (TRPM8): Effect of cAMP, cannabinoid CB1 receptors and endovanilloids

Cited by 135 publications

References 44 publications

Transient receptor potential melastatin 8 channel involvement in the regulation of vascular tone

Transient receptor potential melastatin 8 channel involvement in the regulation of vascular tone

From Phytocannabinoids to Cannabinoid Receptors and Endocannabinoids: Pleiotropic Physiological and Pathological Roles Through Complex Pharmacology

The Endocannabinoid System and its Modulation by Phytocannabinoids

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