Localization and characterization of renal calcitonin receptors by in vitro autoradiography.
Calcitonin receptor binding sites were identified in renal cortex and medulla using the radioligand 125I-salmon calcitonin. Microscopic localization of these receptors revealed binding over medullary and cortical thick ascending limb of the loop of Henle and in distal convoluted tubule. A number of receptor positive cells in the inner medulla were also identified. Characterization of the binding demonstrated a single class of high-affinity binding sites in both the medulla and the cortex with affinity constants of 0.74 +/- 0.09 x 10(9) M-1 and 0.32 +/- 0.05 x 10(9) M-1, respectively, and receptor concentrations of 205 +/- 45 fmol/mg protein and 453 +/- 54 fmol/mg protein, respectively. Competition for 125I-salmon calcitonin binding by a wide range of calcitonin analogs revealed a close correspondence between the reported biological potencies and activities in the current system. The localization of binding sites within the nephron corresponds to the reported localization of calcitonin-stimulated adenylate cyclase activity and suggests that the receptor mediated actions of calcitonin in the kidney utilize cyclic AMP as a second messenger. In addition, the microscopic identification of specific calcitonin receptors helps the delineation of direct actions of this hormone from those which are indirect.
Sexton
P M
PM
University Department of Medicine, Austin Hospital, Heidelberg, Victoria, Australia.
Adam
W R
WR
Moseley
J M
JM
Martin
T J
TJ
Mendelsohn
F A
FA
D000818:Animals; D001345:Autoradiography; D002116:Calcitonin / Q000032:analysis; D007457:Iodine Radioisotopes; D007668:Kidney / Q000032:analysis* / Q000000981:diagnostic imaging; D007672:Kidney Cortex / Q000032:analysis / Q000000981:diagnostic imaging; D007679:Kidney Medulla / Q000032:analysis / Q000000981:diagnostic imaging; D007684:Kidney Tubules / Q000032:analysis / Q000000981:diagnostic imaging; D008297:Male; D011877:Radionuclide Imaging; D051381:Rats; D011919:Rats, Inbred Strains; D018003:Receptors, Calcitonin; D011956:Receptors, Cell Surface / Q000032:analysis*
D007457:Iodine Radioisotopes; D018003:Receptors, Calcitonin; D011956:Receptors, Cell Surface; D002116:Calcitonin