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Transient Receptor Potential


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  • Capsaicin pre-treatment provides neurovascular protection against neonatal hypoxic-ischemic brain injury in rats. 21725760

    Capsaicin, a transient receptor potential vanilloid 1 (TRPV1) agonist, has recently been shown to provide neuroprotection against brain injury in experimental adult models of cerebral ischemia. Accordingly, in this study, we investigated the way in which capsaicin-mediated TRPV1 modulation could attenuate damage in an experimental hypoxic-ischemic (HI) neonatal brain injury model. The Rice-Vannucci method was used in 10-day-old rat pups by performing unilateral carotid artery ligation followed by 2 h of hypoxia (8% O2 at 37°C). Capsaicin was administered intraperitoneally (0.2 mg/kg or 2.0 mg/kg) at 3 h pre-HI or 1 h post-HI. Post assessment included measurement of infarction volume at 24 and 72 h in addition to an assessment of the vascular dynamics of the middle cerebral artery (MCA) at 6 h post-HI. The results indicated that pre-treatment with capsaicin reduced infarction volume significantly with either low-dose or high-dose treatment. Pre-treatment also improved myogenic tone and decreased apoptotic changes in the distal MCA. We concluded that capsaicin pre-treatment may provide neurovascular protection against neonatal HI.
    Tipo de documento:
    Referencia
    Referencia del producto:
    MAB377
    Nombre del producto:
    Anti-NeuN Antibody, clone A60

  • Transient receptor potential vanilloid type 1 channel (TRPV1) immunolocalization in the murine enteric nervous system is affected by the targeted C-terminal epitope of th ... 23482327

    The expression of transient receptor potential vanilloid type 1 channel (TRPV1) in the enteric nervous system is still the subject of debate. Although a number of studies have reported that TRPV1 is limited to extrinsic afferent fibers, other studies argue for an intrinsic expression of TRPV1. In the present study, reverse transcriptase PCR was employed to establish the expression of TRPV1 mRNA throughout the gastrointestinal tract. Using two antibodies directed against different epitopes of TRPV1, we were able to show at the protein level that the observed distribution pattern of TRPV1 is dependent on the antibody used in the immunohistochemical staining. A first antibody indeed mainly stained neuronal fibers, whereas a second antibody exclusively stained perikarya of enteric neurons throughout the mouse gastrointestinal tract. We argue that these different distribution patterns are due to the antibodies discriminating between different modulated forms of TRPV1 that influence the recognition of the targeted immunogen and as such distinguish intracellular from plasmalemmal forms of TRPV1. Our study is the first to directly compare these two antibodies within the same species and in identical conditions. Our observations underline that detailed knowledge of the epitope that is recognized by the antibodies employed in immunohistochemical procedures is a prerequisite for correctly interpreting experimental results.
    Tipo de documento:
    Referencia
    Referencia del producto:
    Múltiplo
    Nombre del producto:
    Múltiplo

  • Endogenous prolactin generated during peripheral inflammation contributes to thermal hyperalgesia. 21777304

    Prolactin (PRL) is a hormone and a neuromodulator. It sensitizes TRPV1 (transient receptor potential cation channel subfamily V member 1) responses in sensory neurons, but it is not clear whether peripheral inflammation results in the release of endogenous PRL, or whether endogenous PRL is capable of acting as an inflammatory mediator in a sex-dependent manner. To address these questions, we examined inflammation-induced release of endogenous PRL, and its regulation of thermal hyperalgesia in female and male rats. PRL is expressed in several types of peripheral neuronal and non-neuronal cells, including TRPV1-positive nerve fibers, preadipocytes and activated macrophages/monocytes localized in the vicinity of nerves. Evaluation of PRL levels in hindpaws and plasma indicated that complete Freund's adjuvant (CFA) stimulates release of peripheral, but not systemic, PRL within 6-48 h in both ovariectomized females with estradiol replacement (OVX-E) and intact male rats. The time course of release varies in OVX-E and intact male rats. We next employed the prolactin receptor (PRL-R) antagonist Δ1-9-G129R-hPRL to assess the role of locally produced PRL in nociception. Applied at a ratio of 1 : 1 (PRL:Δ1-9-G129R-hPRL; 40 nm each), this antagonist was able to nearly (≈ 80%) reverse PRL-induced sensitization of capsaicin responses in rat sensory neurons. CFA-induced inflammatory thermal hyperalgesia in OVX-E rat hindpaws was significantly reduced in a dose-dependent manner by the PRL-R antagonist at 6 h but not at 24 h. In contrast, PRL contributed to inflammatory thermal hyperalgesia in intact male rats at 24, but not at 6 h. These findings indicate that inflammation leads to accumulation of endogenous PRL in female and male rats. Furthermore, PRL acts as an inflammatory mediator at different time points for female and intact male rats.
    Tipo de documento:
    Referencia
    Referencia del producto:
    Múltiplo
    Nombre del producto:
    Múltiplo

  • Distribution and function of polycystin-2 in mouse retinal ganglion cells. 22155264

    The polycystin family of transient receptor potential (TRP) channels form Ca(2+) regulated cation channels with distinct subcellullar localizations and functions. As part of heteromultimeric channels and multi-protein complexes, polycystins control intracellular Ca(2+) signals and more generally the translation of extracellular signals and stimuli to intracellular responses. Polycystin-2 channels have been cloned from retina, but their distribution and function in retinal ganglion cells (RGCs) have not yet been established. In the present study, we determined cellular and subcellular localization as well as functional properties of polycystin-2 channels in RGCs. Polycystin-2 expression and distribution in RGCs was assessed by immunohistochemistry on vertical cryostat section of mouse retina as well as primary cultured mouse RGCs, using fluorescence microscopy. Biophysical and pharmacological properties of polycystin-2 channels isolated from primary cultured RGCs were determined using planar lipid bilayer electrophysiology. We detected polycystin-2 immunoreactivity both in the ganglion cell layer as well as in primary cultured RGCs. Subcellular analysis revealed strong cytosolic localization pattern of polycystin-2. Polycystin-2 channel current was Ca(2+) activated, had a maximum slope conductance of 114 pS, and could be blocked in a dose-dependent manner by increasing concentrations of Mg(2+). The cytosolic localization of polycystin-2 in RGCs is in accordance with its function as intracellular Ca(2+) release channel. We conclude that polycystin-2 forms functional channels in RGCs, of which biophysical and pharmacological properties are similar to polycystin-2 channels reported for other tissues and organisms. Our data suggest a potential role for polycystin-2 in RGC Ca(2+) signaling.
    Tipo de documento:
    Referencia
    Referencia del producto:
    AB9088
    Nombre del producto:
    Anti-Polycystin-2 Antibody

  • Parvalbumin and TRPV1 receptor expression in dorsal root ganglion neurons after acute peripheral inflammation. 19397388

    Expression of parvalbumin (PV) and transient receptor potential vanilloid (TRPV1) receptors in the lumbar dorsal root ganglion neurons (DRG) was evaluated in control animals and in rats after acute carageenan-induced knee joint inflammation. PV is a calcium binding protein that acts as a calcium buffer, affects intracellular calcium homeostasis and may thus influence signal transduction and synaptic transmission. TRPV1 receptors are viewed as molecular integrators of nociceptive stimuli and modulate spinal cord synaptic transmission beside their function in the peripheral nerve endings. In naive rats, 13 % of the L4 DRG neurons had PV immunopositivity (PV+) and 36 % expressed TRPV1 receptors (TRPV1+). The soma of the PV+ neurons was of medium to large size, while the TRPV1 receptors were expressed in small diameter neurons. The co-localization of the PV and TRPV1 immunoreactivity was minimal (0.2 %). There was no significant change in the PV+ (11 %), TRPV1+ (42 %) and PV+TRPV1+ (0.25 %) expression, or shift in the neuronal size distribution 28 h after the unilateral peripheral inflammation, both when compared to controls and when ipsilateral to contralateral sides were evaluated. Thus under the given experimental conditions, no change in somatic TRPV1 receptors and PV expression in L4 DRG neurons was found.
    Tipo de documento:
    Referencia
    Referencia del producto:
    AB5370
    Nombre del producto:
    Anti-Capsaicin Receptor Antibody, CT

  • Ultrastructural analysis of the synaptic connectivity of TRPV1-expressing primary afferent terminals in the rat trigeminal caudal nucleus. 20878780

    Trigeminal primary afferents that express the transient receptor potential vanilloid 1 (TRPV1) are important for the transmission of orofacial nociception. However, little is known about how the TRPV1-mediated nociceptive information is processed at the first relay nucleus in the central nervous system (CNS). To address this issue, we studied the synaptic connectivity of TRPV1-positive (+) terminals in the rat trigeminal caudal nucleus (Vc) by using electron microscopic immunohistochemistry and analysis of serial thin sections. Whereas the large majority of TRPV1+ terminals made synaptic contacts of an asymmetric type with one or two postsynaptic dendrites, a considerable fraction also participated in complex glomerular synaptic arrangements. A few TRPV1+ terminals received axoaxonic contacts from synaptic endings that contained pleomorphic synaptic vesicles and were immunolabeled for glutamic acid decarboxylase, the synthesizing enzyme for the inhibitory neurotransmitter γ-aminobutyric acid (GABA). We classified the TRPV1+ terminals into an S-type, containing less than five dense-core vesicles (DCVs), and a DCV-type, containing five or more DCVs. The number of postsynaptic dendrites was similar between the two types of terminals; however, whereas axoaxonic contacts were frequent on the S-type, the DCV-type did not receive axoaxonic contacts. In the sensory root of the trigeminal ganglion, TRPV1+ axons were mostly unmyelinated, and a small fraction was small myelinated. These results suggest that the TRPV1-mediated nociceptive information from the orofacial region is processed in a specific manner by two distinct types of synaptic arrangements in the Vc, and that the central input of a few TRPV1+ afferents is presynaptically modulated via a GABA-mediated mechanism.
    Tipo de documento:
    Referencia
    Referencia del producto:
    AB1511

  • Molecular cloning of a widely expressed human homologue for the Drosophila trp gene. 7589464

    The Drosophila transient receptor potential (trp) gene and its homologue, trpl, have been suggested to mediate calcium entry during the insect's phototransduction process. We isolated a human cDNA, human trp-1 (Htrp-1), encoding a polypeptide of 793 amino acids that is 37% identical (62% similar) to Drosophila trp and trpl. Northern analysis showed that the Htrp-1 transcript is approximately 5.5 kb and expressed in most human tissues, with higher amounts in ovary, testis, heart, and brain. Isolation of Htrp-1 suggests that a trp-type protein is present in mammals and should provide a useful tool in studying calcium-depletion induced calcium influx processes.
    Tipo de documento:
    Referencia
    Referencia del producto:
    AB5574-200UL

  • Evidence for specific TRPM8 expression in human prostate secretory epithelial cells: functional androgen receptor requirement. 15947109

    TRPM8 (melastatine-related transient receptor potential member 8), a member of the transient receptor potential (TRP) superfamily of cation channels, has been shown to be a calcium-channel protein. TRPM8 mRNA has also been shown to be overexpressed in prostate cancer and is considered to play an important role in prostate physiology. This study was designed to determine the androgen-regulation mechanisms for TRPM8 mRNA expression and to identify the phenotype of TRPM8-expressing cells in the human prostate. Our findings show that trpm8 gene expression requires a functional androgen receptor. Furthermore, this article argues strongly in favour of the fact that the trpm8 gene is a primary androgen-responsive gene. Single-cell reverse transcriptase PCR and immunohistochemical experiments also showed that the trpm8 gene was mainly expressed in the apical secretory epithelial cells of the human prostate and trpm8 down-regulation occurred during the loss of the apical differentiated phenotype of the primary cultured human prostate epithelial cells. The androgen-regulated trpm8 expression mechanisms are important in understanding the progression of prostate cancer to androgen-independence. These findings may contribute to design a strategy to predict prostate cancer status from the TRPM8 mRNA level. Furthermore, as the TRPM8 channel is localized in human prostate cells, it will be interesting to understand its physiological function in the normal prostate and its potential role in prostate cancer development.
    Tipo de documento:
    Referencia
    Referencia del producto:
    Múltiplo
    Nombre del producto:
    Múltiplo

  • Capsaicin-induced vasodilatation in human nasal vasculature is mediated by modulation of cyclooxygenase-2 activity and abrogated by sulprostone. 21523557

    Extensively based on evidence gained from experimental animal models, the transient receptor potential vanilloid receptor type 1 (TRPV1)-activator capsaicin is regarded as a valuable tool in the research on neurogenic inflammation. Although capsaicin-related drugs gained renewed interest as a therapeutic tool, there is also controversy as whether neurogenic inflammation actually takes place in humans. In this study, we verified the involvement of capsaicin in vascular responses that are regarded to be implicated in the cascade of neurogenic inflammatory mechanisms. By means of ex vivo functional experiments on human nasal mucosal vascular beds, the effect and mechanism of action of capsaicin was assessed in the absence and presence of various agents that interfere with potentially related transduction pathways. Ten micromolars of capsaicin induced vasodilatations that were reduced by the selective EP(1) prostanoid receptor antagonist SC19220 (10 μM) and almost abolished by the selective COX-2 inhibitor NS398 (1 μM) and the EP(1/3) receptor agonist sulprostone (0.1-10 nM), but not affected by the TRPV1-antagonists capsazepine (5 μM), the neurokinin NK(1) receptor antagonist GR20517A (1 μM), and the calcitonin-gene-related peptide (CGRP) receptor antagonist CGRP8-37 (100 nM). Spontaneously released PGE(2) and PGD(2) levels were significantly reduced in the presence of capsaicin. In conclusion, capsaicin-at concentrations clinically applied or under investigation for diverse disease backgrounds-induces a vasodilatory response in human nasal mucosa via a mechanism involving TRPV1-independent reduction of PGE(2) production by modulation of COX-2 enzymatic activity. These vasodilatations can be suppressed by the EP(1/3) receptor agonist sulprostone at subnanomolar concentrations.
    Tipo de documento:
    Referencia
    Referencia del producto:
    AB5370
    Nombre del producto:
    Anti-Capsaicin Receptor Antibody, CT

  • Intrathecal injection of TRPV1 shRNA leads to increases in blood pressure in rats. 21518266

    The transient receptor potential vanilloid type 1 (TRPV1) channels have been implicated to play a role in blood pressure regulation. However, contribution of tissue specific TRPV1 to blood pressure regulation is largely unknown. Here, we test the hypothesis that TRPV1 expressed in dorsal root ganglia (DRG) of lower thoracic and upper lumbar segments (T8-L3) of the spinal cord and their central and peripheral terminals constitutes a counter regulatory mechanism preventing the increases in blood pressure.The expression of TRPV1 was knocked down by intrathecal injection of TRPV1 short-hairpin RNA (shRNA) in rats. Systolic blood pressure and mean arterial pressure (MAP) were recorded. The level of TRPV1 and tyrosine hydroxylase (TH) was measured by Western blot.Intrathecal injection of TRPV1 shRNA (6 μg kg(-1) day(-1) ) for 3 days increased systolic blood pressure and MAP when compared to rats that received control shRNA (control shRNA: 112 ± 2 vs. TRPV1 shRNA: 123 ± 2 mmHg). TRPV1 expression was suppressed in T8-L3 segments of dorsal horn and DRG as well as mesenteric arteries of rats given TRPV1 shRNA. Contents of TH, a marker of sympathetic nerves, were increased in mesenteric arteries of rats treated with TRPV1 shRNA. Pretreatment with the α1-adrenoceptor blocker, prazosin (1 mg kg(-1) day(-1) , p.o.), abolished the TRPV1 shRNA-induced pressor effects.Our data show that selective knockdown of TRPV1 expressed in DRG of T8-L3 segments of the spinal cord and their central and peripheral terminals increases blood pressure, suggesting that neuronal TRPV1 in these segments possesses a tonic anti-hypertensive effect possibly via suppression of the sympathetic nerve activity.
    Tipo de documento:
    Referencia
    Referencia del producto:
    AB5566
    Nombre del producto:
    Anti-Capsaicin Receptor Antibody, CT