{"title":"Ca2+感应受体-瞬时受体电位介导的Ca2+内流对弯曲细胞外酸度的敏感性。3个内皮细胞。","authors":"Iat-Lon Leong, Chung-Ming Yu, Lian-Ru Shiao, Paul Chan, King-Chuen Wu, Yuk-Man Leung","doi":"10.4103/0304-4920.365460","DOIUrl":null,"url":null,"abstract":"<p><p>Ca<sup>2+</sup>-sensing receptors (CaSRs) are G protein-coupled receptors activated by elevated concentrations of extracellular Ca<sup>2+</sup>. In our previous works, we showed protein and functional expression of CaSR in mouse cerebral endothelial cell (EC) (bEND.3); the CaSR response (high Ca<sup>2+</sup>-elicited cytosolic [Ca<sup>2+</sup>] elevation) was unaffected by suppression of phospholipase C but in part involved Ca<sup>2+</sup> influx through transient receptor potential V1 (TRPV1) channels. In this work, we investigated if extracellular acidity affected CaSR-mediated Ca<sup>2+</sup> influx triggered by high (3 mM) Ca<sup>2+</sup> (CaSR agonist), 3 mM spermine (CaSR agonist), and 10 mM cinacalcet (positive allosteric modulator of CaSR). Extracellular acidosis (pH 6.8 and pH 6.0) strongly suppressed cytosolic [Ca<sup>2+</sup>] elevation triggered by high Ca<sup>2+</sup>, spermine, and cinacalcet; acidosis also inhibited Mn<sup>2+</sup> influx stimulated by high Ca<sup>2+</sup> and cinacalcet. Purinoceptor-triggered Ca<sup>2+</sup> response, however, was not suppressed by acidosis. Extracellular acidity also did not affect membrane potential, suggesting suppressed CaSR-mediated Ca<sup>2+</sup> influx in acidity did not result from the reduced electrical driving force for Ca<sup>2+</sup>. Our results suggest Ca<sup>2+</sup> influx through a putative CaSR-TRP complex in bEND.3 EC was sensitive to extracellular pH.</p>","PeriodicalId":10251,"journal":{"name":"Chinese Journal of Physiology","volume":"65 6","pages":"277-281"},"PeriodicalIF":1.4000,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Sensitivity of Ca<sup>2+</sup>-sensing receptor-transient receptor potential-mediated Ca<sup>2+</sup> influx to extracellular acidity in bEND.3 endothelial cells.\",\"authors\":\"Iat-Lon Leong, Chung-Ming Yu, Lian-Ru Shiao, Paul Chan, King-Chuen Wu, Yuk-Man Leung\",\"doi\":\"10.4103/0304-4920.365460\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Ca<sup>2+</sup>-sensing receptors (CaSRs) are G protein-coupled receptors activated by elevated concentrations of extracellular Ca<sup>2+</sup>. In our previous works, we showed protein and functional expression of CaSR in mouse cerebral endothelial cell (EC) (bEND.3); the CaSR response (high Ca<sup>2+</sup>-elicited cytosolic [Ca<sup>2+</sup>] elevation) was unaffected by suppression of phospholipase C but in part involved Ca<sup>2+</sup> influx through transient receptor potential V1 (TRPV1) channels. In this work, we investigated if extracellular acidity affected CaSR-mediated Ca<sup>2+</sup> influx triggered by high (3 mM) Ca<sup>2+</sup> (CaSR agonist), 3 mM spermine (CaSR agonist), and 10 mM cinacalcet (positive allosteric modulator of CaSR). Extracellular acidosis (pH 6.8 and pH 6.0) strongly suppressed cytosolic [Ca<sup>2+</sup>] elevation triggered by high Ca<sup>2+</sup>, spermine, and cinacalcet; acidosis also inhibited Mn<sup>2+</sup> influx stimulated by high Ca<sup>2+</sup> and cinacalcet. Purinoceptor-triggered Ca<sup>2+</sup> response, however, was not suppressed by acidosis. Extracellular acidity also did not affect membrane potential, suggesting suppressed CaSR-mediated Ca<sup>2+</sup> influx in acidity did not result from the reduced electrical driving force for Ca<sup>2+</sup>. Our results suggest Ca<sup>2+</sup> influx through a putative CaSR-TRP complex in bEND.3 EC was sensitive to extracellular pH.</p>\",\"PeriodicalId\":10251,\"journal\":{\"name\":\"Chinese Journal of Physiology\",\"volume\":\"65 6\",\"pages\":\"277-281\"},\"PeriodicalIF\":1.4000,\"publicationDate\":\"2022-11-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Chinese Journal of Physiology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.4103/0304-4920.365460\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"PHYSIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Chinese Journal of Physiology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.4103/0304-4920.365460","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"PHYSIOLOGY","Score":null,"Total":0}
Sensitivity of Ca2+-sensing receptor-transient receptor potential-mediated Ca2+ influx to extracellular acidity in bEND.3 endothelial cells.
Ca2+-sensing receptors (CaSRs) are G protein-coupled receptors activated by elevated concentrations of extracellular Ca2+. In our previous works, we showed protein and functional expression of CaSR in mouse cerebral endothelial cell (EC) (bEND.3); the CaSR response (high Ca2+-elicited cytosolic [Ca2+] elevation) was unaffected by suppression of phospholipase C but in part involved Ca2+ influx through transient receptor potential V1 (TRPV1) channels. In this work, we investigated if extracellular acidity affected CaSR-mediated Ca2+ influx triggered by high (3 mM) Ca2+ (CaSR agonist), 3 mM spermine (CaSR agonist), and 10 mM cinacalcet (positive allosteric modulator of CaSR). Extracellular acidosis (pH 6.8 and pH 6.0) strongly suppressed cytosolic [Ca2+] elevation triggered by high Ca2+, spermine, and cinacalcet; acidosis also inhibited Mn2+ influx stimulated by high Ca2+ and cinacalcet. Purinoceptor-triggered Ca2+ response, however, was not suppressed by acidosis. Extracellular acidity also did not affect membrane potential, suggesting suppressed CaSR-mediated Ca2+ influx in acidity did not result from the reduced electrical driving force for Ca2+. Our results suggest Ca2+ influx through a putative CaSR-TRP complex in bEND.3 EC was sensitive to extracellular pH.
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