Abstract
Oral NaCl produces a greater natriuresis and diuresis as compared with an intravenous infusion of the same amount of NaCl, indicating the existence of a gastro-renal axis. Gastrin is the major gastrointestinal hormone, which could be taken up by the renal proximal tubule (RPT) cells. We hypothesized that gastrin and dopamine receptors in the kidney interact to synergistically increase sodium excretion, an impaired interaction may be involved in the pathogenesis of hypertension. In Wistar-Kyoto (WKY) rats, infusion of gastrin induced a natriuresis and diuresis, which was abrogated in the presence of CI-988, a gastrin receptor (CCK B R) antagonist, as well as SCH 23390, a D 1 -like receptor antagonist. Similarly, the natriuretic and diuretic effect of fenoldopam, a D 1 -like receptor agonist, was blocked by SCH23390 , as well as CI-988. However, the natriuretic effects of gastrin and fenoldopam were not observed in spontaneously hypertensive rats (SHRs). The gastrin/D 1 -like receptor interaction was also confirmed in RPT cells. In RPT cells from WKY but not SHRs, stimulation of either D 1 -like receptor or gastrin receptor inhibited Na + -K + -ATPase activity, an effect that was blocked by the presence of SCH23390 or CI-988. In RPT cells from WKY and SHRs, CCK B R and D 1 R co-immunoprecipitated, which were increased after stimulation of either D 1 R or CCK B R receptor in WKY cells, but not in SHR cells. Stimulation of one receptor increased RPT cell membrane expression of another receptor. The data suggest that there is a synergism between CCK B R and D 1 -like receptor to increase sodium excretion. Aberrant interaction between the renal CCK B R and D 1 -like receptors (e.g., D 1 R) may play a role in the pathogenesis of hypertension.
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