title: The calcium sensing receptor modulates fluid reabsorption and acid secretion in the proximal tubule.
abstract: The proximal tubule uses a complex process of apical acid secretion and basolateral bicarbonate absorption to regulate both luminal acidification and fluid absorption. One of the primary regulators of apical acid secretion is the luminal sodium-hydrogen exchanger expressed along the apical membrane of the proximal tubule. Similarly, the calcium-sensing receptor (CaSR) is also located along the luminal membrane of the proximal tubule. Here we investigated the role of CaSR in proton secretion and fluid reabsorption in proximal tubules by modulating luminal calcium concentration, using both in vivo micropuncture in rats and in vitro perfused mouse proximal tubules. Using CaSR knockout mice and a calcimimetic agent, we found that increased proton secretion and fluid reabsorption were CaSR dependent. Activating CaSR by either raising the luminal calcium ion concentration or by the calcimimetic caused a concomitant increase in sodium-dependent proton extrusion and fluid reabsorption, whereas in proximal tubules isolated from CaSR knockout mice varying calcium ion concentration had no effect. Application of a calcimimetic in lower concentrations of calcium ion stimulated these processes in vitro and in vivo. Thus, in both rats and mice, increased luminal calcium concentration leads to enhanced fluid reabsorption in the proximal tubule, a process related to activation of CaSR.
authors.affiliation: Department of Nephrology, Second University of Naples, Naples, Italy.
authors.forename: Giovambattista
authors.initials: G
authors.lastname: Capasso
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Geibel
authors.forename: Sara
authors.initials: S
authors.lastname: Damiano
authors.forename: Philippe
authors.initials: P
authors.lastname: Jaeger
authors.forename: William G
authors.initials: WG
authors.lastname: Richards
authors.forename: John P
authors.initials: JP
authors.lastname: Geibel
mesh_terms: D000136:Acid-Base Equilibrium / Q000187:drug effects; D000818:Animals; D057966:Calcimimetic Agents / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D010477:Perfusion; D011677:Punctures; D051381:Rats; D017207:Rats, Sprague-Dawley; D044169:Receptors, Calcium-Sensing / Q000819:agonists / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000819:agonists / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: C577923:CASR protein, mouse; D057966:Calcimimetic Agents; C523486:Gcm2 protein, mouse; D009687:Nuclear Proteins; D044169:Receptors, Calcium-Sensing; D043562:Receptors, G-Protein-Coupled; D017923:Sodium-Hydrogen Exchangers; D014157:Transcription Factors; C473605:extracellular calcium cation-sensing receptor, rat; D002118:Calcium