LOCALIZATION OF ANGIOTENSIN-II TYPE-1 RECEPTOR SUBTYPE MESSENGER-RNA IN RAT-KIDNEY

The physiological effects of angiotensin II (ANG II) on the kidney are mediated primarily by the ANG II type 1 (AT(1)) receptor. Two highly similar AT(1) receptor subtypes have been identified in the rat by mol ecular cloning techniques, namely AT(1A) and AT(1B). The intrarenal lo calization of the AT(1A) and AT(1B) receptor subtypes has not been stu died by hybridization methods with subtype-specific receptor probes. U sing radiolabeled probes from the 3' noncoding region of the AT(1A) an d AT(1B) cDNAs, we localized AT(1) mRNA in rat kidney by in situ hybri dization. Specificity of the 3' noncoding region probes was tested by Northern blot and solution hybridization methods. AT(1A) mRNA levels w ere highest in the liver, kidney, and adrenal. In contrast, AT(1B) mRN A levels were highest in the adrenal and pituitary and low in kidney. Autoradiographic localization of I-125-[Sar(1),Ile(8)]ANG II binding i ndicated that the highest levels of AT(1) receptors were found in glom eruli and vascular elements. In situ hybridization with a nonselective AT(1) receptor riboprobe indicated that the highest levels of AT(1) m RNA were in the outer medullary vasa recta and cortical glomeruli with additional diffuse labeling of the cortex and outer medulla, consiste nt with labeling of tubular elements. In contrast, in situ hybridizati on with the AT(1) subtype selective probes revealed that AT(1A) recept or mRNA was primarily localized to the vasa recta and diffusely to the outer stripe of the outer medulla and the renal cortex. The highest l evels of AT(1B) mRNA were localized to the tip of the papilla correspo nding to the ureter with low levels found within the vasa recta. These results indicate that the AT(1A) receptor subtype is the major form o f AT(1) receptor expressed in rat kidney but leaves open the possibili ty that additional AT(1) receptors may be expressed in glomeruli.