LOCALIZATION AND DEGRADATION OF CALCITONIN IN RENAL PROXIMAL TUBULE OF RAT VISUALIZED BY IMMUNOCYTOCHEMISTRY

Immunocytochemical and cryoultramicrotomy techniques were applied to l abel endogenous as well as intravenously injected calcitonin (CT) in r at kidney. Endogenous CT was located to the membranes of the brush bor der, endocytotic invaginations and vacuoles and dense apical tubules s uggesting degradation at the brush border and/or within endocytotic va cuoles after glomerular filtration of endogeneous CT. There was no lab eling at the basolateral membranes indicating that possible basolatera l binding sites are of minor quantitative importance in degradation. A fter injection of human CT there was an additional labeling of lysosom es whereas injection of insulin did not change the labeling pattern fo r endogenous CT indicating that the uptake of CT involves specific bin ding sites. Quantitative immunocytochemistry after injection of h-CT a pplying monoclonal antibodies against two different fragments of CT sh owed that the relative amounts of these fragments differed in vacuoles and lysosomes from that observed in the brush border, but no differen ce was seen in dense apical tubules. This suggests that injected CT ma y be degraded both at the brush border, within endocytotic vacuoles an d lysosomes and that some fragments are more sensitive to hydrolysis i n lysosomes than others. Furthermore, it indicates an early formation of dense apical tubules before detectable degradation of CT occurs in endocytotic vacuoles.