Interaction of angiotensin II type 1 and D5 dopamine receptors in renal proximal tubule cells

Angiotensin II type 1 (AT(1)) receptor and D-1 and D-3 dopamine receptors directly interact in renal proximal tubule (RPT) cells from normotensive Wistar-Kyoto rats (WKY). There is indirect evidence for a D-5 and AT(1) receptor interaction in WKY and spontaneously hypertensive rats (SHR). Therefore, we sought direct evidence of an interaction between AT(1) and D-5 receptors in RPT cells. D-5 and AT(1) receptors colocalized in WKY cells. Angiotensin II decreased D-5 receptors in WKY cells in a time- and concentration-dependent manner (EC50 = 2.7 x 10(-9) M; t(1/2) = 4.9 hours), effects that were blocked by an AT(1) receptor antagonist (losartan). In SHR, angiotensin II (10(-8) M/24 hours) also decreased D-5 receptors (0.96 +/- 0.08 versus 0.72 +/- 0.08; n = 12) and to the same degree as in WKY cells (1.44 +/- 0.07 versus 0.92 +/- 0.08). However, basal D-5 receptors were decreased in SHR RPT cells (SHR 0.96 +/- 0.08; WKY 1.44 +/- 0.07; n = 12 per strain; P < 0.05) and renal brush border membranes of SHR compared with WKY (SHR 0.54 +/- 0.16 versus WKY 1.46 +/- 0.10; n = 5 per strain; P < 0.05). Angiotensin II decreased AT(1) receptor expression in WKY (1.00 +/- 0.04 versus 0.72 +/- 0.08; n +/- 8; P < 0.05) but increased it in SHR (0.96 +/- 0.04 versus 1.32 +/- 0.08; n = 8; P < 0.05). AT(1) and D-5 receptors also interacted in vivo; renal D-5 receptor protein was higher in mice lacking the AT(1A) receptor (AT(1A)-/-; 1.61 +/- 0.31; n = 6) than in wild-type littermates used as controls (AT(1A)+/+; 0.81 +/- 0.08; n = 6; P < 0.05), and renal cortical AT(1) receptor protein was higher in D-5 receptor null mice than in wild-type littermates (1.18 +/- 0.08 versus 0.84 +/- 0.07; n = 4; P < 0.05). We conclude that D-5 and AT(1) receptors interact with each other. Altered interactions between AT(1) and dopamine receptors may play a role in the pathogenesis of hypertension.