Deletion of the pH Sensor GPR4 Decreases Renal Acid Excretion
Proton receptors are G protein-coupled receptors that accept protons as ligands and function as pH sensors. One of the proton receptors, GPR4, is relatively abundant in the kidney, but its potential role in acid-base homeostasis is unknown. In this study, we examined the distribution of GPR4 in the...
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| Veröffentlicht in: | Journal of the American Society of Nephrology 2010-10, Vol.21 (10), p.1745-1755 |
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| creator | XUMING SUN YANG, Li V TIEGS, Brian C AREND, Lois J MCGRAW, Dennis W PENN, Raymond B PETROVIC, Snezana |
| description | Proton receptors are G protein-coupled receptors that accept protons as ligands and function as pH sensors. One of the proton receptors, GPR4, is relatively abundant in the kidney, but its potential role in acid-base homeostasis is unknown. In this study, we examined the distribution of GPR4 in the kidney, its function in kidney epithelial cells, and the effects of its deletion on acid-base homeostasis. We observed GPR4 expression in the kidney cortex, in the outer and inner medulla, in isolated kidney collecting ducts, and in cultured outer and inner medullary collecting duct cells (mOMCD1 and mIMCD3). Cultured mOMCD1 cells exhibited pH-dependent accumulation of intracellular cAMP, characteristic of GPR4 activation; GPR4 knockdown attenuated this accumulation. In vivo, deletion of GPR4 decreased net acid secretion by the kidney and resulted in a nongap metabolic acidosis, indicating that GPR4 is required to maintain acid-base homeostasis. Collectively, these findings suggest that GPR4 is a pH sensor with an important role in regulating acid secretion in the kidney collecting duct. |
| doi_str_mv | 10.1681/asn.2009050477 |
| format | Article |
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One of the proton receptors, GPR4, is relatively abundant in the kidney, but its potential role in acid-base homeostasis is unknown. In this study, we examined the distribution of GPR4 in the kidney, its function in kidney epithelial cells, and the effects of its deletion on acid-base homeostasis. We observed GPR4 expression in the kidney cortex, in the outer and inner medulla, in isolated kidney collecting ducts, and in cultured outer and inner medullary collecting duct cells (mOMCD1 and mIMCD3). Cultured mOMCD1 cells exhibited pH-dependent accumulation of intracellular cAMP, characteristic of GPR4 activation; GPR4 knockdown attenuated this accumulation. In vivo, deletion of GPR4 decreased net acid secretion by the kidney and resulted in a nongap metabolic acidosis, indicating that GPR4 is required to maintain acid-base homeostasis. Collectively, these findings suggest that GPR4 is a pH sensor with an important role in regulating acid secretion in the kidney collecting duct.</description><identifier>ISSN: 1046-6673</identifier><identifier>EISSN: 1533-3450</identifier><identifier>DOI: 10.1681/asn.2009050477</identifier><identifier>PMID: 20798260</identifier><identifier>CODEN: JASNEU</identifier><language>eng</language><publisher>Washington, DC: American Society of Nephrology</publisher><subject>Acid-Base Equilibrium ; Acidosis, Renal Tubular - metabolism ; Acids - metabolism ; Animals ; Basic Research ; Biological and medical sciences ; Cell Line ; Cyclic AMP - metabolism ; Humans ; Hydrogen-Ion Concentration ; Kidney Tubules, Collecting - metabolism ; Kidney Tubules, Collecting - secretion ; Medical sciences ; Mice ; Mice, Knockout ; Nephrology. Urinary tract diseases ; Receptors, G-Protein-Coupled - genetics ; Receptors, G-Protein-Coupled - metabolism ; RNA, Messenger - metabolism</subject><ispartof>Journal of the American Society of Nephrology, 2010-10, Vol.21 (10), p.1745-1755</ispartof><rights>2015 INIST-CNRS</rights><rights>Copyright © 2010 by the American Society of Nephrology</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c485t-72c1b2b079cd17de9ccd6b3ae913ec9e59bf1cac3f6e311b0e8e2015d318118c3</citedby><cites>FETCH-LOGICAL-c485t-72c1b2b079cd17de9ccd6b3ae913ec9e59bf1cac3f6e311b0e8e2015d318118c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3013533/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3013533/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=23285322$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20798260$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>XUMING SUN</creatorcontrib><creatorcontrib>YANG, Li V</creatorcontrib><creatorcontrib>TIEGS, Brian C</creatorcontrib><creatorcontrib>AREND, Lois J</creatorcontrib><creatorcontrib>MCGRAW, Dennis W</creatorcontrib><creatorcontrib>PENN, Raymond B</creatorcontrib><creatorcontrib>PETROVIC, Snezana</creatorcontrib><title>Deletion of the pH Sensor GPR4 Decreases Renal Acid Excretion</title><title>Journal of the American Society of Nephrology</title><addtitle>J Am Soc Nephrol</addtitle><description>Proton receptors are G protein-coupled receptors that accept protons as ligands and function as pH sensors. One of the proton receptors, GPR4, is relatively abundant in the kidney, but its potential role in acid-base homeostasis is unknown. In this study, we examined the distribution of GPR4 in the kidney, its function in kidney epithelial cells, and the effects of its deletion on acid-base homeostasis. We observed GPR4 expression in the kidney cortex, in the outer and inner medulla, in isolated kidney collecting ducts, and in cultured outer and inner medullary collecting duct cells (mOMCD1 and mIMCD3). Cultured mOMCD1 cells exhibited pH-dependent accumulation of intracellular cAMP, characteristic of GPR4 activation; GPR4 knockdown attenuated this accumulation. In vivo, deletion of GPR4 decreased net acid secretion by the kidney and resulted in a nongap metabolic acidosis, indicating that GPR4 is required to maintain acid-base homeostasis. Collectively, these findings suggest that GPR4 is a pH sensor with an important role in regulating acid secretion in the kidney collecting duct.</description><subject>Acid-Base Equilibrium</subject><subject>Acidosis, Renal Tubular - metabolism</subject><subject>Acids - metabolism</subject><subject>Animals</subject><subject>Basic Research</subject><subject>Biological and medical sciences</subject><subject>Cell Line</subject><subject>Cyclic AMP - metabolism</subject><subject>Humans</subject><subject>Hydrogen-Ion Concentration</subject><subject>Kidney Tubules, Collecting - metabolism</subject><subject>Kidney Tubules, Collecting - secretion</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>Nephrology. Urinary tract diseases</subject><subject>Receptors, G-Protein-Coupled - genetics</subject><subject>Receptors, G-Protein-Coupled - metabolism</subject><subject>RNA, Messenger - metabolism</subject><issn>1046-6673</issn><issn>1533-3450</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkM1PwkAQxTdGI4hePZq9GE_F_ejutgdNCCCYEDWg5812O5Wa0uJuMfrfWwRBTzOZ-c17k4fQOSVdKiN6bXzZZYTERJBQqQPUpoLzgIeCHDY9CWUgpeItdOL9GyFUMKWOUYsRFUdMkja6GUABdV6VuMpwPQe8HOMZlL5yePQ0DfEArAPjweMplKbAPZunePjZDNdHp-goM4WHs23toJe74XN_HEweR_f93iSwYSTqQDFLE5Y0pjalKoXY2lQm3EBMOdgYRJxk1BrLMwmc0oRABKx5NuU0ojSyvINuN7rLVbKA1EJZO1PopcsXxn3pyuT6_6bM5_q1-tCcUN4E0ghcbQVc9b4CX-tF7i0UhSmhWnmthJQijn_I7oa0rvLeQbZzoUSvI9e92YPeR94cXPz9bYf_ZtwAl1vAeGuKzJnS5n7PcRYJzhj_BphNiPs</recordid><startdate>20101001</startdate><enddate>20101001</enddate><creator>XUMING SUN</creator><creator>YANG, Li V</creator><creator>TIEGS, Brian C</creator><creator>AREND, Lois J</creator><creator>MCGRAW, Dennis W</creator><creator>PENN, Raymond B</creator><creator>PETROVIC, Snezana</creator><general>American Society of Nephrology</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20101001</creationdate><title>Deletion of the pH Sensor GPR4 Decreases Renal Acid Excretion</title><author>XUMING SUN ; YANG, Li V ; TIEGS, Brian C ; AREND, Lois J ; MCGRAW, Dennis W ; PENN, Raymond B ; PETROVIC, Snezana</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c485t-72c1b2b079cd17de9ccd6b3ae913ec9e59bf1cac3f6e311b0e8e2015d318118c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Acid-Base Equilibrium</topic><topic>Acidosis, Renal Tubular - metabolism</topic><topic>Acids - metabolism</topic><topic>Animals</topic><topic>Basic Research</topic><topic>Biological and medical sciences</topic><topic>Cell Line</topic><topic>Cyclic AMP - metabolism</topic><topic>Humans</topic><topic>Hydrogen-Ion Concentration</topic><topic>Kidney Tubules, Collecting - metabolism</topic><topic>Kidney Tubules, Collecting - secretion</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Knockout</topic><topic>Nephrology. Urinary tract diseases</topic><topic>Receptors, G-Protein-Coupled - genetics</topic><topic>Receptors, G-Protein-Coupled - metabolism</topic><topic>RNA, Messenger - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>XUMING SUN</creatorcontrib><creatorcontrib>YANG, Li V</creatorcontrib><creatorcontrib>TIEGS, Brian C</creatorcontrib><creatorcontrib>AREND, Lois J</creatorcontrib><creatorcontrib>MCGRAW, Dennis W</creatorcontrib><creatorcontrib>PENN, Raymond B</creatorcontrib><creatorcontrib>PETROVIC, Snezana</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of the American Society of Nephrology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>XUMING SUN</au><au>YANG, Li V</au><au>TIEGS, Brian C</au><au>AREND, Lois J</au><au>MCGRAW, Dennis W</au><au>PENN, Raymond B</au><au>PETROVIC, Snezana</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Deletion of the pH Sensor GPR4 Decreases Renal Acid Excretion</atitle><jtitle>Journal of the American Society of Nephrology</jtitle><addtitle>J Am Soc Nephrol</addtitle><date>2010-10-01</date><risdate>2010</risdate><volume>21</volume><issue>10</issue><spage>1745</spage><epage>1755</epage><pages>1745-1755</pages><issn>1046-6673</issn><eissn>1533-3450</eissn><coden>JASNEU</coden><abstract>Proton receptors are G protein-coupled receptors that accept protons as ligands and function as pH sensors. One of the proton receptors, GPR4, is relatively abundant in the kidney, but its potential role in acid-base homeostasis is unknown. In this study, we examined the distribution of GPR4 in the kidney, its function in kidney epithelial cells, and the effects of its deletion on acid-base homeostasis. We observed GPR4 expression in the kidney cortex, in the outer and inner medulla, in isolated kidney collecting ducts, and in cultured outer and inner medullary collecting duct cells (mOMCD1 and mIMCD3). Cultured mOMCD1 cells exhibited pH-dependent accumulation of intracellular cAMP, characteristic of GPR4 activation; GPR4 knockdown attenuated this accumulation. In vivo, deletion of GPR4 decreased net acid secretion by the kidney and resulted in a nongap metabolic acidosis, indicating that GPR4 is required to maintain acid-base homeostasis. 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| subjects | Acid-Base Equilibrium Acidosis, Renal Tubular - metabolism Acids - metabolism Animals Basic Research Biological and medical sciences Cell Line Cyclic AMP - metabolism Humans Hydrogen-Ion Concentration Kidney Tubules, Collecting - metabolism Kidney Tubules, Collecting - secretion Medical sciences Mice Mice, Knockout Nephrology. Urinary tract diseases Receptors, G-Protein-Coupled - genetics Receptors, G-Protein-Coupled - metabolism RNA, Messenger - metabolism |
| title | Deletion of the pH Sensor GPR4 Decreases Renal Acid Excretion |
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