Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Transient Receptor Potential Channels”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,027 records · Page 57Linked to original sources
PubMed2006

Hyposmotic stimulation-induced nitric oxide production in outer hair cells of the guinea pig cochlea.

Nitric oxide (NO) production during hyposmotic stimulation in outer hair cells (OHCs) of the guinea pig cochlea was investigated using the NO sensitive dye DAF-2. Simultaneous measurement of the cell length and NO production showed rapid hyposmotic-induced cell swelling to precede NO production in OHCs. Hyposmotic stimulation failed to induce NO production in the Ca(2+)-free solution. L-N(G)-nitroarginine methyl ester (L-NAME), a non-specific NO synthase inhibitor and gadolinium, a stretch-activated channel blocker inhibited the hyposmotic stimulation-induced NO production whereas suramin, a P2 receptor antagonist did not. S-nitroso-N-acetylpenicillamine (SNAP), a NO donor inhibited the hyposmotic stimulation-induced increase in the intracellular Ca(2+) concentrations ([Ca(2+)](i)) while L-NAME enhanced it. 1H-[1,2,4]oxadiazole[4,3a]quinoxalin-1-one, an inhibitor of guanylate cyclase and KT5823, an inhibitor of cGMP-dependent protein kinase (PKG) mimicked effects of L-NAME on the Ca(2+) response. Transient receptor potential vanilloid 4 (TRPV4), an osmo- and mechanosensitive channel was expressed in the OHCs by means of immunohistochemistry. 4alpha-phorbol 12,13-didecanoate, a TRPV4 synthetic activator, induced NO production in OHCs. These results suggest that hyposmotic stimulation can induce NO production by the [Ca(2+)](i) increase, which is presumably mediated by the activation of TRPV4 in OHCs. NO conversely inhibits the Ca(2+) response via the NO-cGMP-PKG pathway by a feedback mechanism.

Animals↗
PubMed1996

The roles of trp and calcium in regulating photoreceptor function in Drosophila.

Invertebrate photoreceptors use the ubiquitous inositol-lipid signaling pathway for phototransduction. This pathway depends on Ca2+ release from internal stores and on Ca2+ entry via light-activated channels to replenish the loss of Ca2+ in those stores. The Drosophila transient receptor potential (TRP) protein is essential for the high Ca2+ permeability and other biophysical properties of these light-activated channels, which affect both excitation and adaptation in photoreceptor cells. Physiological and heterologous expression studies indicate that TRP is a putative subunit of a surface membrane channel that can be activated by depletion of internal Ca2+ stores. Furthermore, trp is an archetypal member of a multigene family whose products share a structure that is highly conserved throughout evolution, from worms to humans.

Adaptation, Ocular↗
PubMed2006

Presenilin mutations linked to familial Alzheimer's disease cause an imbalance in phosphatidylinositol 4,5-bisphosphate metabolism.

Phosphatidylinositol 4,5-bisphosphate (PIP2) is an important cellular effector whose functions include the regulation of ion channels and membrane trafficking. Aberrant PIP2 metabolism has also been implicated in a variety of human disease states, e.g., cancer and diabetes. Here we report that familial Alzheimer's disease (FAD)-associated presenilin mutations cause an imbalance in PIP2 metabolism. We find that the transient receptor potential melastatin 7 (TRPM7)-associated Mg2+ -inhibited cation (MIC) channel underlies ion channel dysfunction in presenilin FAD mutant cells, and the observed channel deficits are restored by the addition of PIP2, a known regulator of the MIC/TRPM7 channel. Lipid analyses show that PIP2 turnover is selectively affected in FAD mutant presenilin cells. We also find that modulation of cellular PIP2 closely correlates with 42-residue amyloid beta-peptide (Abeta42) levels. Our data suggest that PIP2 imbalance may contribute to Alzheimer's disease pathogenesis by affecting multiple cellular pathways, such as the generation of toxic Abeta42 as well as the activity of the MIC/TRPM7 channel, which has been linked to other neurodegenerative conditions. Thus, our study suggests that brain-specific modulation of PIP2 may offer a therapeutic approach in Alzheimer's disease.

Alzheimer Disease↗
PubMed2006

Contribution of TRPM8 channels to cold transduction in primary sensory neurons and peripheral nerve terminals.

Transient receptor potential melastatin 8 (TRPM8) is the best molecular candidate for innocuous cold detection by peripheral thermoreceptor terminals. To dissect out the contribution of this cold- and menthol-gated, nonselective cation channel to cold transduction, we identified BCTC [N-(4-tert-butylphenyl)-4-(3-chloropyridin-2-yl)piperazine-1-carboxamide] as a potent and full blocker of recombinant TRPM8 channels. In cold-sensitive trigeminal ganglion neurons of mice and guinea pig, responses to menthol were abolished by BCTC. In contrast, the effect of BCTC on cold-evoked responses was variable but showed a good correlation with the presence or lack of menthol sensitivity in the same neuron, suggesting a specific blocking action of BCTC on TRPM8 channels. The biophysical properties of native cold-gated currents (I(cold)), and the currents blocked by BCTC were nearly identical, consistent with a role of this channel in cold sensing at the soma. The temperature activation threshold of native TRPM8 channels was significantly warmer than those reported in previous expression studies. The effect of BCTC on native I(cold) was characterized by a dose-dependent shift in the temperature threshold of activation. The role of TRPM8 in transduction was further investigated in the guinea pig cornea, a peripheral territory densely innervated with cold thermoreceptors. All cold-sensitive terminals were activated by menthol, suggesting the functional expression of TRPM8 channels in their membrane. However, the spontaneous activity and firing pattern characteristic of cold thermoreceptors was totally immune to TRPM8 channel blockade with BCTC or SKF96365 (1-[2-(4-methoxyphenyl)-2-[3-(4-methoxyphenyl)propoxy]ethyl-1H-imidazole hydrochloride). Cold-evoked responses in corneal terminals were also essentially unaffected by these drugs, whereas responses to menthol were completely abolished. The minor impairment in the ability to transduce cold stimuli by peripheral corneal thermoreceptors during TRPM8 blockade unveils an overlapping functional role for various thermosensitive mechanisms in these nerve terminals.

Animals↗
PubMed1984

Adrenergic-cholinergic interactions on membrane potential of K+ -depolarized ventricular muscle.

In guinea pig ventricular muscles exposed to K+-rich (27 mM) Tyrode solution containing 0.2 mM Ba, catecholamine elicited a slight depolarization of the resting membrane. Application of acetylcholine (ACh) during this catecholamine-induced response caused a repolarization, and removal of ACh induced a transient enhancement in the depolarization (rebound). These effects of ACh were abolished by atropine. Application of ACh alone and its removal had little effect on the membrane potential. Like the catecholamine-induced depolarization, the rebound depolarization after ACh removal was inhibited by slow channel blockers. Thus the rebound was attributed at least in part to enhanced changes in the catecholamine-sensitive conductance, i.e., a beta-receptor-mediated increase in the slow channel conductance. In driven muscles perfused with normal Tyrode solution, there was a rebound increase in twitch tension when ACh was removed in the presence of catecholamine, and this rebound was accompanied by an "extra" elevation of the action potential plateau. Thus cessation of the stimulation of myocardial muscarinic receptors may transiently lead to an enhanced activity of the beta-adrenoceptor-slow channel system in guinea pig ventricular muscle.

Acetylcholine↗
PubMed1995

Sodium channels and GABAA receptor-channel complex as targets of environmental toxicants.

Voltage-activated sodium channels and GABAA receptor-chloride channel complex are among the most important target sites of various environmental neurotoxicants. Pyrethroids keep the sodium channels open for prolonged periods of time leading to hyperexcitation of the entire nervous system. In rat cerebellar Purkinje neurons and dorsal root ganglion neurons, only about 1% of sodium channel population needed to be modified by the pyrethroid tetramethrin to increase the depolarizing after-potential to the level of the threshold membrane potential for generation of repetitive after-discharges. This concept of toxicity amplification is applicable to other chemicals that go through a threshold phenomenon to exert their effects. The potency of pyrethroids on neuronal sodium channels increased with lowering the temperature with a Q10 value of 0.2. The selective pyrethroid toxicity between mammals and insects can be quantitatively explained on the basis of the differences in 5 factors, i.e. the intrinsic sodium channel sensitivity, the sodium channel modification due to temperature difference, the reversibility of sodium channel, the detoxication of pyrethroids, and body size. These 5 factors are multiplied to approximately 2000 which is in the same order of magnitude as that of the difference in LD50. Dieldrin had a dual action on the GABAA receptor-chloride channel complex of rat dorsal root ganglion neurons. The initial transient potentiation of GABA-induced currents after application of dieldrin was followed by a suppression. Dieldrin-induced potentiation of current was observed only when the gamma 2 subunit was present in embryonic kidney cells (HEK-293) transfected with GABA receptor subunits. Dieldrin-induced suppression was observed in the presence and absence of the gamma 2 subunit. The dieldrin suppression of GABA-induced currents is deemed directly responsible for hyperactive symptoms of poisoning in animals.

Animals↗
PubMed2002

Possible coupling of prostaglandin E receptor EP(1) to TRP5 expressed in Xenopus laevis oocytes.

We previously reported that the prostaglandin E(2) (PGE(2)) receptor subtype EP(1) is coupled to intracellular Ca(2+) mobilization in CHO cells, which is dependent on extracellular Ca(2+) in a pertussis toxin-insensitive manner [H. Katoh, et al., Biochim. Biophys. Acta 1244 (1995) 41-48]. However, it remains unknown about the signal transduction involved in this response. To investigate the mechanism regulating Ca(2+) mobilization mediated by EP(1) receptors in detail, we performed a series of experiments using the Xenopus laevis oocyte expression system and found that endogenous G(q) and/or G(11), and not G(i1) is involved in the Ca(2+) mobilization induced by PGE(2). We further investigated the receptor-activated Ca(2+) channel (RACC)-related response by introducing mRNA for mouse transient receptor potential 5 (TRP5), a possible candidate for the RACC, and found effective coupling between them. These results suggest that the EP(1) receptors induce Ca(2+) mobilization via G(q) and/or G(11) and Ca(2+) influx via TRP.

Animals↗
PubMed2005

Formation of a physiological complex between TRPV2 and RGA protein promotes cell surface expression of TRPV2.

The transient receptor potential, sub-family Vanilloid (TRPV)(2) cation channel is activated in response to extreme temperature elevations in sensory neurons. However, TRPV2 is widely expressed in tissues with no sensory function, including cells of the immune system. Regulation of GRC, the murine homolog of TRPV2 has been studied in insulinoma cells and myocytes. GRC is activated in response to certain growth factors and neuropeptides, via a mechanism that involves regulated access of the channel to the plasma membrane. This is likely to be an important primary control mechanism for TRPV2 outside the CNS. Here, we report that a regulated trafficking step controls the access of TRPV2 to the cell surface in mast cells. In mast cells, elevations in cytosolic cAMP are sufficient to drive plasma membrane localization of TRPV2. We have previously proposed that the recombinase gene activator protein (RGA), a four-transmembrane domain, intracellular protein, associates with TRPV2 during the biosynthesis and early trafficking of the channel. We use a polyclonal antibody to RGA to confirm the formation of a physiological complex between RGA and TRPV2. Finally, we show that over-expression of the RGA protein potentiates the basal surface localization of TRPV2. We propose that trafficking and activation mechanisms intersect for TRPV2, and that cAMP mobilizing stimuli may regulate TRPV2 localization in non-sensory cells. RGA participates in the control of TRPV2 surface levels, and co-expression of RGA may be a key component of experimental systems that seek to study TRPV2 physiology.

Animals↗
PubMed2006

TRPV1 (vanilloid receptor) in the urinary tract: expression, function and clinical applications.

The transient receptor potential vanilloid subfamily 1 (TRPV1) is an ion channel activated by capsaicin, heat, protons and endogenous ligands such as anandamide. It is largely expressed in the urinary tract of mammals. Structures in which the receptor expression is firmly established include sensory fibers and urothelial cells, although the presence of TRPV1 in other cell types has been reported. As in other systems, pain perception was the first role attributed to TRPV1 in the urinary tract. However, it is now increasingly clear that TRPV1 also regulates the frequency of bladder reflex contractions, either through direct excitation of sensory fibers or through urothelial-sensory fiber cross talk involving the release of neuromediators from the epithelial cells. In addition, the recent identification of the receptor in urothelial and prostatic cancer cells raise the exciting hypothesis that TRPV1 is involved in cell differentiation. Desensitization of the receptor by capsaicin and resiniferatoxin has been investigated for therapeutic purposes. For the moment, lower urinary tract dysfunctions in which some benefit was obtained include painful bladder syndrome and overactive bladder of neurogenic and non-neurogenic origin. However, desensitization may become obsolete when non-toxic, potent TRPV1 antagonists become available.

Animals↗
PubMed2006

The transient receptor potential vanilloid 1: role in airway inflammation and disease.

The transient receptor potential vanilloid 1 (TRPV1) is an excitatory cation channel, rather selectively expressed in a subpopulation of nociceptive, primary sensory neurons that promote neurogenic inflammation via neuropeptide release. TRPV1 is activated by noxious temperature, low extracellular pH and diverse lipid derivatives, and is uniquely sensitive to vanilloid molecules, including capsaicin. TRPV1 expression and sensitivity is highly regulated by diverse G protein-coupled and tyrosine kinase receptors. Other exogenous or endogenous chemical agents, including reactive oxygen species, ethanol and hydrogen sulphide sensitize/activate TRPV1. In the airways, TRPV1 agonists cause cough, bronchoconstriction, microvascular leakage, hyperreactivity and hypersecretion. Patients with asthma and chronic obstructive pulmonary disease are more sensitive to the tussive effect of TRPV1 agonists and TRPV1 activation may contribute to respiratory symptoms caused by acidic media present in the airways during asthma exacerbation, gastroesophageal reflux induced asthma or in other conditions. TRPV1 antagonists may be useful in the treatment of these diseases.

Animals↗
PubMed2005

TRPV1 regulators mediate gentamicin penetration of cultured kidney cells.

Transient receptor potential (TRP) receptors are, typically, calcium-permeant cation channels that transduce environmental stimuli. Both kidney epithelial and inner ear sensory cells express TRPV1, are mechanosensors and accumulate the aminoglycoside antibiotic gentamicin. Recently, we showed that Texas Red-conjugated gentamicin (GTTR) enters kidney cells via an endosome-independent pathway. Here, we used GTTR to investigate this non-endocytotic mechanism of gentamicin uptake. In serum-free buffers, GTTR penetrated MDCK cells within 30 s and uptake was modulated by extracellular, multivalent cations (Ca2+, La3+, Gd3+) or protons. We verified the La3+ modulation of GTTR uptake using immunocytochemical detection of unconjugated gentamicin. Membrane depolarization, induced by high extracellular K+ or valinomycin, also reduced GTTR uptake, suggesting electrophoretic permeation through ion channels. GTTR uptake was enhanced by the TRPV1 agonists, resiniferatoxin and anandamide, in Ca2+-free media. Competitive antagonists of the TRPV1 cation current, iodo-resiniferatoxin and SB366791, also enhanced GTTR uptake independently of Ca2+, reinforcing these antagonists' potential as latent agonists in specific situations. Ruthenium Red blocked GTTR uptake in the presence or absence of these TRPV1-agonists and antagonists. In addition, GTTR uptake was blocked by RTX in the presence of more physiological levels (2 mM) of Ca2+. Thus gentamicin enters cells via cation channels, and gentamicin uptake can be modulated by regulators of the TRPV1 channel.

Anilides↗
PubMed2006

TRPC6 in glomerular health and disease: what we know and what we believe.

Mutations in TRPC6, a member of the transient receptor potential (TRP) superfamily of non-selective cation channels, have been identified as causing a familial form of focal segmental glomerulosclerosis, a disease characterized by proteinuria and progressive renal failure. Here we review the effect of disease-associated mutations on TRPC6 function and place TRPC6 within the context of other proteins central to glomerular and podocyte function. Finally, the known roles of TRPC6 in the kidney and other organ systems are used as a framework to discuss possible signaling pathways that TRPC6 may modulate during normal glomerular function and in disease states.

Animals↗
PubMed2005

Transient receptor potential vanilloid (TRPV-1) promotes neurogenic inflammation in the pancreas via activation of the neurokinin-1 receptor (NK-1R).

OBJECTIVES: The transient receptor potential vanilloid 1 (TRPV-1) is an ion channel found on primary sensory afferent neurons. Activation of TRPV-1 leads to the release of the proinflammatory neuropeptide substance P (SP). SP then binds to the neurokinin-1 receptor (NK1-R) on endothelial cells and promotes extravasation of plasma and proteins into the interstitial tissue and neutrophil infiltration, a process called neurogenic inflammation. We tested 2 hypotheses: (1) activation of TRPV-1 in the pancreas leads to interstitial edema and neutrophil infiltration and (2) TRPV-1-induced plasma extravasation is mediated by the release of SP and activation of the NK1-R in the rat. METHODS: We measured extravasation of the intravascular tracer Evans blue as an index of plasma extravasation and quantified pancreas tissue myeloperoxidase activity (MPO) as a marker of neutrophil infiltration. The severity of inflammation following intravenous infusion of the secretagogue cerulein (10 microg/kg/h x 4 hours) was assessed using a histologic scoring system. RESULTS: Intravenous injection of the TRPV-1 agonist capsaicin induced a dose-dependent increase in Evans blue accumulation in the rat pancreas (P < 0.05 vs. vehicle control). This effect was blocked by pretreatment with the TRPV-1 antagonist capsazepine (1.8 mg/kg), or the NK1-R antagonist CP 96,345 (1 mg/kg). Capsazepine also reduced cerulein-induced Evans blue, MPO, and histologic severity of inflammation in the pancreas but had no effect on serum amylase. CONCLUSION: Activation of TRPV-1 induces SP-mediated plasma extravasation in the rat pancreas via activation of the NK1-R. TRPV-1 mediates neurogenic inflammation in cerulein-induced pancreatitis in the rat.

Animals↗
PubMed2005

Extensive co-localization and heteromultimer formation of the vanilloid receptor-like protein TRPV2 and the capsaicin receptor TRPV1 in the adult rat cerebral cortex.

The capsaicin receptor TRPV1, a member of the transient receptor potential (TRP) family of calcium-selective ion channels, responds to noxious stimuli and is predominantly expressed in nociceptive neurons. The homologous receptor TRPV2 shows wide tissue distribution including some sensory neurons, where it is proposed to function as a heat sensor or a growth-factor-activated channel. Members of the TRP family of channels have been shown to interact, resulting in hybrid channels with new properties. We examined the possibility of multimer formation between TRPV1 and TRPV2, using biochemical techniques. We present evidence that TRPV1 and TRPV2 can heteromultimerize efficiently in vitro. By using immunohistochemistry we detected co-localization of the two receptors in rat dorsal root ganglia. TRPC4 transcripts are also detected in capsaicin-sensitive dorsal root ganglia neurons. We extended the search for TRPV1-TRPV2 co-localization in the brain, where we detected extensive co-expression of the two receptors in the IV, V and VI layer neurons of the adult rat cerebral cortex. Co-immunoprecipitation experiments confirmed the interaction of the two receptors in vivo, indicating heteromultimer formation in native tissue. Formation of heteromultimers between vanilloid receptors may increase the functional diversity of this receptor family.

Animals↗
PubMed2004

Inhibition of glutamate-induced delayed calcium deregulation by 2-APB and La3+ in cultured cortical neurones.

Exposure of neurones in culture to excitotoxic levels of glutamate results in an initial transient spike in [Ca2+]i followed by a delayed, irreversible [Ca2+]i rise governed by rapid kinetics, with Ca2+ originating from the extracellular medium. The molecular mechanism responsible for the secondary Ca2+ rise is unknown. Here, we report that the delayed Ca2+ entry in cortical neurones is diminished by 2-aminoethoxydiphenyl borate (2-APB: IC50 = 62 +/- 9 microm) and La3+ (IC50 = 7.2 +/- 3 microm), both known to inhibit transient receptor potential (TRP) and store-operated Ca2+ (SOC) channels. Application of thapsigargin, however, failed to exacerbate the delayed Ca2+ deregulation, arguing against a store depletion event as the stimulus for induction of the secondary [Ca2+]i rise. In addition, these neurones did not exhibit SOC entry. Unexpectedly, application of ryanodine or caffeine significantly inhibited glutamate-induced delayed Ca2+ deregulation. In basal Ca2+ entry experiments, La3+ and 2-APB modulated the rapid rise in [Ca2+]i caused by exposure of neurones to Ca2+ after pre-incubating in a calcium-free medium. This basal Ca2+ influx was mitigated by extracellular Mg2+ but not aggravated by thapsigargin, ryanodine or caffeine. These results indicate that 2-APB and La3+ influence non-store-operated Ca2+ influx in cortical neurones and that this route of Ca2+ entry is involved in glutamate-induced delayed Ca2+ deregulation.

Animals↗
PubMed2005

Role of transient receptor potential vanilloid 1 receptors in adjuvant-induced chronic arthritis: in vivo study using gene-deficient mice.

The transient receptor potential vanilloid 1 (TRPV1) receptor is a nonselective cation channel localized on a subset of primary sensory neurons and can be activated by a wide range of stimuli. The present study investigated the role of this receptor in chronic arthritis evoked by complete Freund's adjuvant (CFA) using TRPV1 receptor gene-deleted (TRPV1-/-) mice and wild-type counterparts (TRPV1+/+). In TRPV1+/+ mice, CFA injected intraplantarly into the left hindpaw and the root of the tail induced swelling of the injected and contralateral paws up to 130 and 28%, respectively, measured by plethysmometry throughout 18 days. Mechanonociceptive threshold measured with dynamic plantar aesthesiometry was decreased by 50 and 18% on the injected and contralateral paws, respectively. Histological examination and scoring of the tibiotarsal joints revealed marked arthritic changes in wild-type mice. In TRPV1-/- animals edema, histological score and mechanical allodynia were significantly smaller. Daily treatment with the lipoxygenase inhibitor nordihydroguaretic acid (NDGA), the cyclooxygenase inhibitor indomethacin, the bradykinin B2 receptor antagonist HOE-140 [D-arginyl-L-arginyl-L-prolyl-trans-4-hydroxy-L-prolylglycyl-3-(2-thyenyl)-L-alanyl-L-seryl-D-1,2,2,4-tetrahydro-3-isoquinolinecarbonyl-L-(2a,3b,7ab)-octahydro-1H-indole-2-carbonyl-L-arginine], or the B1 receptor antagonist desArgHOE-140 [D-arginyl-L-arginyl-L-prolyl-trans-4-hydroxy-L-prolylglycyl-3-(2-thyenyl)-L-alanyl-L-seryl-D-1,2,2,4-tetrahydro-3-isoquinolinecarbonyl-L-(2a,3b,7ab)-octahydro-1H-indole-2-carbonyl] was performed to reveal what mediators might activate TRPV1. NDGA significantly inhibited edema, hyperalgesia, and arthritis score in TRPV1+/+, but not in TRPV1-/- mice. The effect of indomethacin was markedly smaller in knockouts. In TRPV1+/+ animals, HOE-140, but not desArgHOE-140, inhibited arthritis, whereas in TRPV1-/- mice, HOE-140 produced limited effect. Thus, whereas bradykinin and lipoxygenase products seem to act exclusively via TRPV1 activation, prostanoids do not, or at least only partially, to enhance murine experimental arthritis and related hyperalgesia.

Animals↗
PubMed2006

Detergent-resistant membrane microdomains in the disposition of the lipid signaling molecule anandamide.

The endogenous cannabinoid anandamide is an agonist of the cannabinoid receptors CB1 and CB2, as well as transient receptor potential vanilloid type 1 and type 4 ion channels. In recent years, there has been a great deal of interest in the cellular processes regulating the signaling of endocannabinoids such as anandamide. This is due largely to evidence that augmentation of cannabinergic tone might be therapeutically beneficial in the treatment of multiple disease states such as chronic pain, anxiety, multiple sclerosis, and neuropsychiatric disorders. Of particular interest are the cellular processes that regulate the cellular accumulation and metabolism of anandamide. Characterization of the process by which anandamide is internalized and metabolized by the cell may identify drug targets useful in the positive modulation of cannabinergic tone. Recently, we reported that detergent-resistant membrane microdomains known as lipid rafts play a role in the cellular accumulation of anandamide by mediating an endocytic process responsible for anandamide internalization. The enzyme primarily responsible for anandamide metabolism, fatty acid amide hydrolase, is excluded from lipid rafts. However, the metabolites of anandamide accumulate in these detergent-resistant membrane microdomains. There is some preliminary evidence that makes it reasonable to propose that anandamide metabolites enriched in lipid rafts may act as precursors to anandamide synthesis. Overall, experimental evidence is mounting that detergent-resistant membrane microdomains such as lipid rafts may play a role in the cellular regulation of anandamide inactivation and production.

Animals↗
PubMed2004

Cellular domains that contribute to Ca2+ entry events.

Stimulation of cell surface receptors that increase phosphatidylinositol 4,5-bisphosphate (PIP2) hydrolysis leads to intracellular Ca2+ release and activation of plasma membrane Ca2+ entry channels. Ca2+ entry via these channels regulates a wide array of physiological functions. The molecular composition of these channels and the mechanisms that activate or inactivate them have not yet been elucidated. Members of the TRPC subfamily of the TRP (transient receptor potential) family of proteins have been recently suggested as molecular components of these channels. In addition, Ca2+ signaling proteins and the signals they generate are compartmentalized and spatiotemporally regulated. Thus, the mechanisms involved in the assembly and trafficking of Ca2+ signaling proteins, including TRPC channels, will determine the regulation of Ca2+ entry and its effect on cellular function.

Animals↗