RELATIONSHIPS OF NA-ATPASE (NKA) INHIBITORY ACTIVITY IN HUMAN BREAST CYST FLUID( AND K+ CONCENTRATIONS TO GRP, CGRP, AND CALCITONIN IMMUNOREACTIVITIES AND NA+, K+)

Background: Although the etiology of gross cystic disease of the breas t is unknown, elevated cyst concentrations of potassium (K+) (>60 mM/L ) may be related to symptoms. The purpose of this study was to clarify the mechanism(s) of K+ accumulation in breast cysts. Methods: We assa yed cyst fluids for factors known to exert effects on K transport, nam ely, endogenous digitalis-like inhibitors of Na+,K+-ATPase (NKA) and t he neuropeptides gastrin-releasing peptide (GRP), calcitonin (CT), and calcitonin gene-related peptide (CGRP). Results: Cyst fluid K+ was di rectly correlated with cyst volume, cyst NKA inhibitory activity (in o uabain equivalents), and cyst concentrations of calcitonin, GRP, and C GRP. Cyst fluid Na+ was inversely correlated with cyst fluid K+, cyst NKA inhibitory activity, cyst volume, and cyst fluid concentrations of calcitonin. GRP, and CGRP. NKA inhibitory activity correlated directl y with GRP and CGRP. Immunocytochemistry localized GRP to breast cyst lining cells and areas of ductal and lobular epithelial hyperplasia in biopsies of 15 of 15 cysts and in 5 of 5 breast carcinomas, but not i n (0 of 5) normal breast biopsies. Specificity of GRP staining was dem onstrated by total abolition of reactivity after adsorption with synth etic GRP, but not after adsorption with synthetic substance P, neuroki nin A, or neurokinin B. Conclusions: We conclude that both the concent rations of endogenous digitalis-like factors and the neuropeptides cal citonin, GRP, and CGRP in human breast cyst fluids are related to the concentrations of K+ and Na+ in breast cysts and to cyst volume.