HUMAN SMALL-CELL LUNG-CANCER CELL-LINES EXPRESS FUNCTIONAL ATRIAL-NATRIURETIC-PEPTIDE RECEPTORS

Small cell lung cancer cell (SCLC) lines, NCI-H82, NCI-H660, and NCI-H 1284, and HeLa cells were analyzed for the presence of atrial natriure tic peptide (ANP) receptors. In these SCLC cell lines and HeLa cells, ANP A receptor mRNA was identified by Southern blot analyses or polyme rase chain reaction products and RNase protection assays using poly(A) +-selected RNA. Saturable binding assays revealed that HeLa cells had 2000 to 5000 high affinity atrial natriuretic peptide receptors per ce ll with a dissociation constant of 140 pM. In the SCLC cell lines, the binding was saturable but too low to accurately estimate the number o f binding sites. After addition of human ANP, radioimmunoassays reveal ed accumulation of cyclic GMP in SCLC cells as well as HeLa cells in a dose-dependent fashion. The half-maximal stimulation concentration of cyclic GMP accumulation in HeLa and these SCLC cell lines was approxi mately 2 nM. Tetrazolyl blue assays and tritiated thymidine incorporat ion did not show any remarkable growth inhibition or growth stimulatio n of SCLC cell lines after addition of human ANP up to 3.3 muM, more t han 1000-fold greater than the half-maximal stimulation concentration of cyclic GMP accumulation. Our results indicate that human SCLC cells express functional ANP receptors but ANP addition produced no detecta ble change in their growth pattern.