HUMAN KIDNEY AS TARGET FOR SOMATOSTATIN - HIGH-AFFINITY RECEPTORS IN TUBULES AND VASA-RECTA

Somatostatin (SRIH) receptors were identified in human kidneys by in v itro receptor autoradiography using I-125-[Tyr(3)] octreotide and I-12 5-[Leu(8),D-Trp(22),Tyr(25)] SRIH-28 as radioligands. Characterization of the binding demonstrated a single class of high affinity binding s ites with a dissociation constant (K-d) of 0.5 nmol/L. Binding depende d on GTP and magnesium and sodium concentrations. SRIH-14, SRIH-28, an d octreotide were able to displace the radioligand in the high affinit y range, whereas biologically inactive SRIH analogs or unrelated pepti des were not. Microscopic localization of these receptors revealed bin ding over cortical and medullary areas. In the cortex, the receptors w ere located in the proximal tubules. No SRIH receptors were found in t he glomeruli. In the medulla, the receptors were identified in high de nsity in medullary vasa recta. A diffuse labeling of lesser density ob served in the remaining medulla corresponded to collecting tubules. Th e receptor concentration was 32 fmol/mg protein in the renal cortex an d 304 fmol/mg protein in the vasa recta. The receptors were undetectab le in the rat kidney and are, thus, species dependent. SRIH receptors in the human kidney may be the molecular basis for the actions of SRIH on renal functions and may indicate a therapeutic potential for SRIH analogs in this tissue.