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Hormones and their Effects on the Cardiovascular System
Published in Stephen T. Sinatra, Mark C. Houston, Nutritional and Integrative Strategies in Cardiovascular Medicine, 2015
Pregnenolone also activates transient receptor potential melastatin-3 (TRPM3), which is a calcium-permeable ion channel. TRPM3 is positively coupled to insulin secretion in B cells. One study suggested that TRPM3 is functionally relevant in contractile and proliferating phenotypes of vascular smooth muscle cells, constitutive channel activity, and regulation of cholesterol. Human trials need to be done.228
Neuronal and non-neuronal TRPA1 as therapeutic targets for pain and headache relief
Published in Temperature, 2023
Luigi F. Iannone, Romina Nassini, Riccardo Patacchini, Pierangelo Geppetti, Francesco De Logu
From the initial proposal of TRPA1 as a sensor of cold temperature [13], the channel role in the physiological sensing of temperature changes has been subject to debate, and experiments assessing cold thermo-sensation in non-human cell cultures remain uncertain [25]. Studies using purified human TRPA1 (hTRPA1) inserted into lipid-bilayers showed its intrinsic bidirectional (U-shaped) thermosensor activity that is modified by the redox state and ligands, with different TRPA1 channel conformations involved in cold and heat sensation [26,27]. Therefore, in mammals, TRPA1 may contribute to sensing warmth and uncomfortable heat in addition to noxious cold. Accordingly, a series of findings indicate that TRPA1 can be heat-sensitive in some mammalian somatosensory neurons (in a triad with TRPV1 and TRPM3) and that TRPA1 is implicated in thermal sensation, including heat (in cooperation with TRPV1 and TRPM3) [28]. However, hTRPA1 overexpressed in HEK293 (human embryonic kidney) cells failed to respond to cold stimulus (5°C) thus suggesting a possible not intrinsic activation [29]. Considering that cooling can increase calcium ion influx and that hTRPA1 can be directly activated by calcium ions, an indirect activation by background calcium influx could also be hypothesized [25,30].
TRPA1 as a therapeutic target for nociceptive pain
Published in Expert Opinion on Therapeutic Targets, 2020
Daniel Souza Monteiro de Araujo, Romina Nassini, Pierangelo Geppetti, Francesco De Logu
A variety of receptors in sensory neurons directly encode harmful stimuli that generate propagated action potentials to signal pain. These stimuli consist of physical (mechanical forces, temperature variations) and exogenous (irritants of vegetal origin such as capsaicin, menthol or isothiocyanates) and endogenous (protons, prostaglandins, kinins, and many others) chemical agents. Multi damage events may act indirectly on the nociceptors, via the release of inflammatory substances and the accumulation of inflammatory cells, which favor nociceptor sensitization to any stimulus [117]. In this context, TRP channels have been identified as potential targets and multimodal sensors of irritative and pain signals. In addition, TRP channels may cooperate to encode a specific pain signal, as in the case of noxious heat, which requires the simultaneous contribution of TRPV1, TRPM3, and TRPA1 [118]. More importantly, robust evidence indicates TRPA1 as a major player in mediating the prolonged hypersensitivity to thermal, chemical, and mechanical stimuli detected in models of nociceptive, inflammatory and neuropathic pain [11,15,119-121–122].
An overview of carbonic anhydrases and membrane channels of synoviocytes in inflamed joints
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2019
The Ca2+ entry through TRPM3 is involved in cell survival, death, growth, and differentiation91. Hyaluronan, known as the major component of the extracellular matrix, was increased in RA patients92. The increased secretion of hyaluronan from RA FLS was reduced by TRPM3 activator pregnenolone sulphate, activating TRPM3-mediated Ca2+ entry8193,94. The TRPM7 mediates a variety of functions, such as cell cycle, migration differentiation, and regulation of Ca2+ homeostasis and it is correlated with the oxidative stress-induced cell injury95, 96, 97, 9895–97. It has been proposed that hypoxia and low glucose also lead to ER stress in RA joints98. Inhibition of TRPM7 by Gd3+ and 2-aminoethoxydiphenyl borate (2-APB) induced RA FLS apoptosis by activating ER stress99.