Background
Activation of renal D&sub3; receptor induces natriuresis and diuresis in Wistar-Kyoto (WKY) rats; in the presence of ETB receptor antagonist, the natriuretic effect of D&sub3; receptor in WKY rats is reduced. We hypothesize that ETB receptor activation may regulate D&sub3; receptor expression in renal proximal tubule (RPT) cells from WKY rats, which is impaired in RPT cells from spontaneously hypertensive rats (SHRs).
Conclusion
ETB receptors regulate and physically interact with D&sub3; receptors differently in WKY rats and SHRs. The impaired natriuretic effect in SHRs may be, in part, related to impaired ETB and D&sub3; receptor interactions.
Methods
D&sub3; receptor expression was determined by immunoblotting; the D&sub3;/ETB receptor linkage was checked by coimmunoprecipitation; Na(+)-K(+)-ATPase activity was determined as the rate of inorganic phosphate released in the presence or absence of ouabain.
Results
In RPT cells from WKY rats, the ETB receptor agonist BQ3020 increased D&sub3; receptor protein. In contrast, in RPT cells from SHRs, BQ3020 did not increase D&sub3; receptor. There was coimmunoprecipitation between D&sub3; and ETB receptors in RPT cells from WKY and SHRs. Activation of ETB receptor increased D&sub3;/ETB coimmunoprecipitation in RPT cells from WKY rats, but not from SHRs. The basal levels of D&sub3;/ETB receptor coimmunoprecipitation were greater in RPT cells from WKY rats than in those from SHRs. Stimulation of D&sub3; receptor inhibited Na(+)-K(+)-ATPase activity, which was augmented by the pretreatment with the ETB receptor agonist BQ3020 in WKY RPT cells, but not in SHR RPT cells.