Endothelin-1 binding sites and inositol-monophosphate formation in kidney medulla from adult and juvenile SHR and WKY rats

Abstract

High resolution autoradiography at the cellular level localized endothelin-1 binding sites to the collecting ducts in the rat renal papilla. These receptors were functionally coupled to the phosphatidyl-inositol system since endothelin-1 stimulated the accumulation of IP(1) in a concentration-dependent manner in cross chopped slices from renal papillae. The concentration-effect curves in 4 week old normotensive Wistar-Kyoto rats (WKY) lay to the right of curves from 4 week old and adult spontaneously hypertensive rats (SHR) and adult WKY (20-24 week old) animals; the EC(50) values in the 4 week old animals were 17 +/- 5 and 8 +/- 1 nM (P < 0.05, n = 5; mean +/- SE) for the normotensive and hypertensive animals, respectively. Autoradiographic studies showed that the density and distribution of binding sites for [(125)I]endothelin-1 in the kidneys did not differ between the groups; receptor densities in the renal papillae were 461 +/- 37 (fmol/mg protein) in the 4 week old WKY, and 443 +/- 27 (fmol/mg protein) in the 4 week old SHR. The plasma levels of immunoreactive endothelin-1 were also similar between groups; 4 week old SHR (39 +/- 3 pg/ml) and 4 week old WKY (36 +/- 1 pg/ml). The increased response to endothelin-1 may be related to the development of the hypertensive state in the SHR.