CELLULAR-LOCALIZATION OF ENDOTHELIN RECEPTOR SUBTYPES IN THE RAT-KIDNEY FOLLOWING IN-VITRO LABELING

1. We have previously shown that [I-125]-endothelin (ET) receptor bind ing is localized almost exclusively to the fenestrated endothelial cel ls of glomerular capillaries and peritubular capillaries in the rat ki dney following systemic administration of the radioligand in vivo, Bec ause of the lack of specific ET receptor binding in other glomerular a nd tubular structures following in vivo labelling, we undertook furthe r studies, using electron microscopic autoradiography and ET receptor subtype selective ligands, to investigate whether other renal componen ts also contain ET receptor binding and, if so, to determine the cellu lar localization of the ET receptor subtypes, ET(A) and ET(B), followi ng in vitro labelling. 2. At the electron microscopic level, ET bindin g sites were localized primarily to the fenestrated endothelium of glo merular and peritubular capillaries of the cortex, inner stripe of the outer medulla and the inner medulla. ET binding sites also occurred o verlying renomedullary interstitial cells (RMIC) of the inner medulla. 3. The ET(B) receptor selective agonist, sarafotoxin 6c (S6c), abolis hed ET binding in the vascular endothelium throughout the kidney, whil e the ET(A) receptor selective antagonist, BQ123, was without effect. Both BQ123 and S6c partially inhibited the binding in the RMIC of the inner medulla. 4. These results indicate that ET receptor binding in t he fenestrated endothelium in the glomerular capillaries and peritubul ar capillaries belongs mainly to the ET(B) subtype, whereas both ET(A) and ET(B) subtypes are present in the RMIC.