INTERACTION OF ADRENOMEDULLIN WITH CALCITONIN RECEPTOR IN CULTURED HUMAN BREAST-CANCER CELLS, T-47D

Human adrenomedullin (hADM), human calcitonin gene-related peptide (hC GRP), and salmon calcitonin (sCT)-activated adenylyl cyclase with EC50 , values of 132, 764, and 0.5 nM, respectively, in human breast cancer cell line, T 47D. Treatment of T 47D cell membranes with near maximal concentrations of sCT, hADM and hCGRP had no additive effect on adeny lyl cyclase activity. Salmon calcitonin (8-32)(sCT (8-32)), selective antagonist of calcitonin receptor, inhibited the activation of adenyly l cyclase by these three peptides. On the other hand, the putative ADM receptor antagonist, ADM (22-52), and CGRP receptor antagonist, CGRP (8-37), failed to inhibit ADM-, CGRP- or sCT-activated adenylyl cyclas e. These results suggest that in T47D cells, both ADM and CGRP activat ed adenylyl cyclase through sCT receptors. (C) 1998 Elsevier Science I nc.