Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0847097 (acidity)
 15,165 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Transient receptor potential (TRP) proteins constitute a large non-voltage-gated cation channel superfamily, activated polymodally by various physicochemical stimuli, and are implicated in a variety of cellular functions. Known activators for TRP include not only chemical stimuli such as receptor stimulation, increased acidity and pungent/cooling agents, but temperature change and various forms of mechanical stimuli such as osmotic stress, membrane stretch, and shear force. Recent investigations have revealed that at least ten mammalian TRPs exhibit mechanosensitivity (TRPC1, 5, 6; TRPV1, 2, 4; TRPM3, 7; TRPA1; TRPP2), but the mechanisms underlying it appear considerably divergent and complex. The proposed mechanisms are associated with lipid bilayer mechanics, specialized force-transducing structures, biochemical reactions, membrane trafficking and transcriptional regulation. Many of mechanosensitive (MS)-TRP channel likely undergo multiple regulations via these mechanisms. In the cardiovascular system in which hemodynamic forces constantly operate, the impact of mechanical stress may be particularly significant. Extensive morphological and functional studies have indicated that several MS-TRP channels are expressed in cardiac muscle, vascular smooth muscle, endothelium and vasosensory neurons, each differentially contributing to cardiovascular (CV) functions. To further complexity, the recent evidence suggests that mechanical stress may synergize with neurohormonal mechanisms thereby amplifying otherwise marginal responses. Furthermore, the currently available data suggest that MS-TRP channels may be involved in CV pathophysiology such as cardiac arrhythmia, cardiac hypertrophy/myopathy, hypertension and aneurysms. This review will overview currently known mechanisms for mechanical activation/modulation of TRPs and possible connections of MS-TRP channels to CV disorders.
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PMID:Mechanosensitive TRP channels in cardiovascular pathophysiology. 1950 17

Extracts of Helleborus roots were traditionally used in the Balkan area for their analgesic action. We report that the pure natural product MCS-18 isolated from this source is a potent, specific and reversible antagonist of the capsaicin receptor, TRPV1, expressed in rat dorsal root ganglion (DRG) neurons. TRPV1 is a non-selective cation channel expressed in a subset of cutaneous and visceral sensory nerve endings and activated by noxious heat, acidity and fatty acid metabolites of arachidonic acid, with a decisive role in inflammatory heat hyperalgesia. MCS-18 inhibited the increase in intracellular calcium concentration evoked in DRG neurons by capsaicin (300 nM) and low pH (5.5) but not by heat (43 degrees C). The substance had no effect on the responses mediated by acid-sensing ion channels (ASICs) or the irritant receptor TRPA1. Whole-cell patch-clamp was used to confirm the inhibition of capsaicin-induced currents by MCS-18 which was dose-dependent. The mechanism of inhibition does not require an intact cell, as capsaicin-induced currents were also inhibited in the excised outside-out configuration. The antagonism of the capsaicin and proton action on native TRPV1 by MCS-18 may be of interest for pain therapy.
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PMID:Substance MCS-18 isolated from Helleborus purpurascens is a potent antagonist of the capsaicin receptor, TRPV1, in rat cultured sensory neurons. 1953 33

TRP channels are expressed in taste buds, nerve fibers, and keratinocytes in the oronasal cavity. These channels play integral roles in transducing chemical stimuli, giving rise to sensations of taste, irritation, warmth, coolness, and pungency. Specifically, TRPM5 acts downstream of taste receptors in the taste transduction pathway. TRPM5 channels convert taste-evoked intracellular Ca(2+) release into membrane depolarization to trigger taste transmitter secretion. PKD2L1 is expressed in acid-sensitive (sour) taste bud cells but is unlikely to be the transducer for sour taste. TRPV1 is a receptor for pungent chemical stimuli such as capsaicin and for several irritants (chemesthesis). It is controversial whether TRPV1 is present in the taste buds and plays a direct role in taste. Instead, TRPV1 is expressed in non-gustatory sensory afferent fibers and in keratinocytes of the oronasal cavity. In many sensory fibers and epithelial cells lining the oronasal cavity, TRPA1 is also co-expressed with TRPV1. As with TRPV1, TRPA1 transduces a wide variety of irritants and, in combination with TRPV1, assures that there is a broad response to noxious chemical stimuli. Other TRP channels, including TRPM8, TRPV3, and TRPV4, play less prominent roles in chemesthesis and no known role in taste, per se. The pungency of foods and beverages is likely highly influenced by the temperature at which they are consumed, their acidity, and, for beverages, their carbonation. All these factors modulate the activity of TRP channels in taste buds and in the oronasal mucosa.
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PMID:TRPs in taste and chemesthesis. 2496 71