Objective To examine the role of β-tubulin on the interaction between the cholecystokinin B receptor (CCKBR), dopamine D5 receptor (D5R), and water-sodium metabolism. Methods Normotensive and hypertensive renal proximal tubular cells (RPTC) were equally randomized into three separate groups: a gastrin group, fenoldopam group, and gastrin + nocodazole group. Immunofluorescence was used to determine localization of β-tubulin, CCKBR, and D5R. Western blotting was used to detect CCKBR, D5R, and Na⁺K⁺ -ATP expression. Results Gastrin stimulation in normotensive RPTC increased D5R expression ( P < 0.05) and decreased Na⁺K⁺ -ATP expression ( P < 0.05). These changes were blocked by a tubulin inhibitor ( P < 0.05). However, interaction between CCKBR, D5R, and Na⁺K⁺ -ATP expression was not significantly affected in hypertensive RPTC. Immunofluorescence showed that CCKBR and D5R can induce one another, followed by transport to the plasma membrane, which can prevented by a tubulin inhibitor. Further, tubulin is disordered in hypertensive RPTC, which cannot support intracellular CCKBR and D5R transport. Conclusions tubulin plays a key role in the interaction between CCKBR, D5R, and water-sodium metabolism by improving protein transfer from the cytoplasm to cell membrane.