Decreased responsiveness to chronic salmon calcitonin treatment in rat kidney and calvaria studied using quantitative enzyme cytochemistry.

Abstract

Growing rats were treated with daily im doses of salmon calcitonin (sCT) (2, 15 and 100 IU/kg) for various times (1, 4 and 24 weeks). The effects on intracellular enzyme activities in bone and kidney were monitored using quantitative cytochemical methods previously developed for the identification of specific target tissue responses to calcitonins. The basal alkaline phosphatase activities in both kidney and bone were decreased by long-term treatment at all time periods and doses tested. No change was noted in basal Ca ATPase activities in kidney after treatment. The capacity of target tissues in chronically treated and control rats to respond to an acute iv dose of sCT was also compared. Acute provocation tests in treated and control rats showed that the renal alkaline phosphatase response was decreased in the rats receiving long-term treatment. Moreover, the direction of response was reversed in chronically treated rats when bone alkaline phosphatase and renal Ca-dependent ATPase activity was measured after acute provocation with sCT, i.e. bone alkaline phosphatase was stimulated instead of being inhibited and renal Ca ATPase was inhibited instead of being stimulated. The application of quantitative cytochemical techniques has demonstrated intracellular changes in enzyme activities in both kidney and bone. The impaired sCT responsiveness can be detected at shorter times of treatment (1 week) and lower doses (2 IU/kg) than has previously been possible by measurement of indices of mineral metabolism in plasma or urine.