{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T05:00:51Z","timestamp":1775192451564,"version":"3.50.1"},"reference-count":42,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2016,4,3]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              Ion transport in the renal proximal tubule (\n              <jats:styled-content style=\"fixed-case\">RPT<\/jats:styled-content>\n              ), which is increased in essential hypertension, is regulated by numerous hormones and humoral factors, including insulin and dopamine. Activation of dopamine receptor inhibits sodium reabsorption, whereas activation of insulin receptor increases sodium reabsorption in\n              <jats:styled-content style=\"fixed-case\">RPT<\/jats:styled-content>\n              s, and hyperinsulinemic animals and patients have defective renal dopaminergic system. We presume that there is an inhibition of D\n              <jats:sub>4<\/jats:sub>\n              receptor on insulin receptor expression and effect, and the regulation is lost in spontaneously hypertensive rats (\n              <jats:styled-content style=\"fixed-case\">SHR<\/jats:styled-content>\n              s).\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              Insulin receptor expression was determined by immunoblotting, and Na\n              <jats:sup>+<\/jats:sup>\n              \u2010K\n              <jats:sup>+<\/jats:sup>\n              \u2010\n              <jats:styled-content style=\"fixed-case\">ATP<\/jats:styled-content>\n              ase activity was detected in both Wistar\u2010Kyoto (\n              <jats:styled-content style=\"fixed-case\">WKY<\/jats:styled-content>\n              ) and\n              <jats:styled-content style=\"fixed-case\">SHR RPT<\/jats:styled-content>\n              cells. Stimulation of D\n              <jats:sub>4<\/jats:sub>\n              receptor with\n              <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>\n              168077 decreased expression of insulin receptors, which was blocked in the presence of the calcium\u2010channel blocker, nicardipine (10\n              <jats:sup>\u22126<\/jats:sup>\n              \u00a0mol\/L per 24\u00a0hours), in cell culture medium without calcium or in the presence of inositol 1,4,5\u2010trisphosphate (\n              <jats:styled-content style=\"fixed-case\">IP<\/jats:styled-content>\n              3) receptor blocker (2\u2010aminoethyl diphenylborinate [2\u2010\n              <jats:styled-content style=\"fixed-case\">ADB]<\/jats:styled-content>\n              ; 10\n              <jats:sup>\u22126<\/jats:sup>\n              \u00a0mol\/L per 24\u00a0hours), indicating that extracellular calcium entry and calcium release from the endoplasmic reticulum were involved in the signal pathway. Stimulation of the insulin receptor stimulated Na\n              <jats:sup>+<\/jats:sup>\n              \u2010K\n              <jats:sup>+<\/jats:sup>\n              \u2010\n              <jats:styled-content style=\"fixed-case\">ATP<\/jats:styled-content>\n              ase activity, whereas pretreatment with\n              <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>\n              168077 for 24\u00a0hours decreased the inhibitory effects of insulin receptor on Na\n              <jats:sup>+<\/jats:sup>\n              \u2010K\n              <jats:sup>+<\/jats:sup>\n              \u2010\n              <jats:styled-content style=\"fixed-case\">ATP<\/jats:styled-content>\n              ase activity in\n              <jats:styled-content style=\"fixed-case\">WKY<\/jats:styled-content>\n              cells. However, in\n              <jats:styled-content style=\"fixed-case\">SHR<\/jats:styled-content>\n              cells, inhibition of D\n              <jats:sub>4<\/jats:sub>\n              receptor on insulin receptor expression and effect were lost.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              Activation of D\n              <jats:sub>4<\/jats:sub>\n              receptor inhibits insulin receptor expression in\n              <jats:styled-content style=\"fixed-case\">RPT<\/jats:styled-content>\n              cells from\n              <jats:styled-content style=\"fixed-case\">WKY<\/jats:styled-content>\n              rats. The aberrant inhibition of D\n              <jats:sub>4<\/jats:sub>\n              receptor on insulin receptor expression and effect might be involved in the pathogenesis of essential hypertension.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.115.002448","type":"journal-article","created":{"date-parts":[[2016,4,23]],"date-time":"2016-04-23T03:23:27Z","timestamp":1461381807000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":16,"title":["Inhibition of D\n            <sub>4<\/sub>\n            Dopamine Receptors on Insulin Receptor Expression and Effect in Renal Proximal Tubule Cells"],"prefix":"10.1161","volume":"5","author":[{"given":"Ye","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing, China"},{"name":"Chongqing Institute of Cardiology, Chongqing, 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China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing, China"},{"name":"Chongqing Institute of Cardiology, Chongqing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongyong","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing, China"},{"name":"Chongqing Institute of Cardiology, Chongqing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chunyu","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing, China"},{"name":"Chongqing Institute of Cardiology, Chongqing, 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