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Proton-sensing G protein-coupled receptors From Wikipedia, the free encyclopedia Jump to: navigation, search Production of cAMP in response to activation of TDAG8 G protein-coupled receptor by low pH. Data from Wang et al, "TDAG8 is a proton-sensing and psychosine-sensitive G-protein-coupled receptor". [1] Proton-sensing G protein-coupled receptors are transmembrane receptors which sense acidic pH and include G2A, GPR4, OGR1 and TDAG8.[2] These G protein-coupled receptors are activated when extracellular pH falls into the range of 6.4-6.8 (typical values are above 7.0). The functional role of the low pH sensitivity of the proton-sensing G protein-coupled receptors is being studied in several tissues where cells respond to conditions of low pH including bone and inflamed tissues. The four known proton-sensing G protein-coupled receptors are Class A receptors in subfamily A15. [edit] Nociception Pain sensation can be initiated by nociceptor cells that are sensory neurons with cell bodies located in the dorsal root ganglia. Some nociceptors respond to low pH and the pH-sensitive amiloride-sensitive cation channel 3 has been described as a modulator of acid-induced pain sensation[3]. However, results with amiloride-sensitive cation channel 3 gene knockout mice suggest that those channels do not fully account for acid-induced pain sensation[4]. Proton-sensing G protein-coupled receptors have been shown to be expressed in small-diameter neurons responsible for nociception where they may play a role in acid-induced pain sensation[5]. [edit] Other functions Mice lacking the Ovarian cancer G protein-coupled receptor 1 gene (OGR1) had slower melanoma growth (KO) than control mice with OGR1 (FL), possibly due to a difference in macrophage activity[6]. Mice lacking each of the four identified proton-sensing GPCRs have been studied[6]. Results so far suggest that these GPCRs might regulate cell proliferation (immune system cells such as lymphocytes and macrophages), but due to redundancy and expression of multiple proton-sensing GPCRs family members in the same cell, multiple gene knockouts are needed. Results for mice lacking OGR1 suggested a possible role for proton-sensing GPCRs in osteoclasts. [edit] References ^ Wang JQ, Kon J, Mogi C, Tobo M, Damirin A, Sato K, Komachi M, Malchinkhuu E, Murata N, Kimura T, Kuwabara A, Wakamatsu K, Koizumi H, Uede T, Tsujimoto G, Kurose H, Sato T, Harada A, Misawa N, Tomura H, Okajima F (2004). "TDAG8 is a proton-sensing and psychosine-sensitive G-protein-coupled receptor". J Biol Chem. 279 (44): 45626–45633. doi:10.1074/jbc.M406966200. PMID 15326175.  ^ Seuwen K, Ludwig MG, Wolf RM (2006). "Receptors for protons or lipid messengers or both?". J. Recept. Signal Transduct. Res. 26 (5-6): 599–610. doi:10.1080/10799890600932220. PMID 17118800.  ^ Chen CC, Zimmer A, Sun WH, Hall J, Brownstein MJ, Zimmer A (2002). "A role for ASIC3 in the modulation of high-intensity pain stimuli". Proc Natl Acad Sci U S A. 99 (13): 8992–7. doi:10.1073/pnas.122245999. PMID 12060708.  ^ Yen YT, Tu PH, Chen CJ, Lin YW, Hsieh ST, Chen CC (2009). "Role of acid-sensing ion channel 3 in sub-acute-phase inflammation". Mol Pain. 2009 Jan 7;5:1 5 (1): 1. doi:10.1186/1744-8069-5-1. PMID 19126241. PMC 2632618. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2632618&tool=pmcentrez.  ^ Huang CW, Tzeng JN, Chen YJ, Tsai WF, Chen CC, Sun WH (2007). "Nociceptors of dorsal root ganglion express proton-sensing G-protein-coupled receptors". Mol. Cell. Neurosci. 36 (2): 195–210. doi:10.1016/j.mcn.2007.06.010. PMID 17720533.  ^ a b Li H, Wang D, Singh LS, Berk M, Tan H, Zhao Z, Steinmetz R, Kirmani K, Wei G, Xu Y (2009). "Abnormalities in Osteoclastogenesis and Decreased Tumorigenesis in Mice Deficient for Ovarian Cancer G Protein-Coupled Receptor 1". PLoS ONE 4 (5): e5705. doi:10.1371/journal.pone.0005705. PMID 19479052.  || flash animation Proton-Proton Animation Shows an animated diagram of the proton-proton chain reaction, which is the dominant fusion reaction in the sun's core. UNL Astronomy / ClassAction / Sun and Solar Energy / Animations Usage Instructions Running this animation on your computer... right-click to download fusion01.swf and fusion01.html to the same directory open the html file in a browser to run the animation Linking to this animation... copy and paste the code below into your webpage or blog: Text Link HTML: - or - Image Link HTML: Putting this animation on your website... upload fusion01.swf to the same directory as your webpage copy and paste the following code into your webpage: Embed HTML: || Online Astronomy eText: The Sun The Proton-Proton Cycle(rough notes from lecture of May 5, 2008, partially supplemented, but very incomplete) The Proton-Proton Cycle The proton-proton cycle is a series of nuclear reactions which convert hydrogen nuclei (protons) into helium nuclei (alpha-particles). All Main Sequence stars do this, in one way or another. For stars like the Sun, the process almost always begins with the collision of two protons, hence its name, the "proton-proton" cycle. In massive stars, the process almost always involves carbon atoms catalyzing the reactions, and in the process being changed from carbon to nitrogen to oxygen, and at the end, back to carbon; hence its name, the "carbon" cycle, or using the abbreviations of the heavy atoms involved, the "CNO" cycle. Each "cycle" can be represented as a "chain" of reactions, proceeding one after the other. Sometimes, only one such chain is involved in a particular reaction, but usually, there are several ways in which particles can combine, which result in more or less the same end. In such a case, the chain which occurs most of the time (and usually produces the most overall energy) is the main chain, and those which occur less frequently are side chains. As an example, let's break the proton-proton cycle into its components. The start of this series of reactions is the collision of two protons, creating a deuteron (a hydrogen nucleus with one proton, as is normal, but with a neutron, as well, which is much less common). Since there are two positive charges on the two protons (one each), and only one on the deuteron, a positive charge must be carried off. In this case, that happens through the emission of a positron, or anti-electron -- a particle of antimatter. The reaction also produces a nearly massless particle, with an energy of 0.42 million electron-volts (MeV), called an electron neutrino (ne):(Main chain start) p+ + p+ -> p+n + e+ + ne (0.42MeV) The positron produced in this reaction will almost immediately combine with a normal electron, resulting in the annihilation of the two particles (the total conversion of their mass into energy), and the creation of two gamma-ray photons, with a combined energy of 1.02 MeV:(Main chain second reaction) e+ + e- -> 2 g (1.02MeV) Occasionally, however (about once for every 400 reactions of the sort shown above), the collision of two protons involves a simultaneous collision with an electron. In this case, the energy normally produced by the positron-electron anniliation is not released as two gamma-rays, but transferred to the electron neutrino, giving it a much higher energy (equal to the combined energy of the two steps shown above):(Side chain start) p+ + p+ + e- -> p+n + ne (1.44 MeV) (more to follow) The normal progression of the proton-proton cycle(Wikimedia Commons image, altered by the author, for this discussion) "Reading" from left to right, two positively charged protons collide, emitting a neutrino (n), a positron (e+) or anti-electron, and a deuteron (np+). The positron soon collides with a normal electron (e-), and suffers an annihilation reaction, in which all of the mass and energy of motion are converted into a single gamma-ray (g) photon. In the next step, the deuteron collides with another proton, emitting another gamma-ray, and forming a light helium nucleus (np+p+). Finally, under normal circumstances, the light helium nucleus collides with another light helium nucleus, creating a normal helium nucleus (nnp+p+) or alpha-particle (a-particle), and emitting two protons. Looking at the two chains, top and bottom, that create the light helium nuclei, six protons are used up, and two are returned, for a net loss of four protons and two electrons, in creating the alpha-particle. (far more to follow) || ||