beta-Adrenergic receptors and adenylate cyclase activity in murine lymphoid cell lines.

Abstract

beta-Adrenergic receptors were determined in sixteen cultured tumor cell lines of T- and B-lymphoid derivation by the binding of the hydrophilic ligand [3H]CGP-12177. The number of receptors per cell varied from less than a hundred to over three thousand. Intracellular cAMP responses to isoproterenol and forskolin were measured for seven cell lines possessing a range of receptor numbers. No direct relationship was found between the isoproterenol-induced elevation of cAMP and the receptor number, and forskolin-induced increases in cAMP varied by more than 100-fold between cell lines. Adenylate cyclase activity was also measured in membrane preparations from the seven cell lines. The T-lymphoma line WEHI-22, the line with the highest receptor number (3700 per cell), showed very little response to any stimulatory agent. With the other four cell lines possessing receptors, the membrane-bound adenylate cyclase activity evoked by isoproterenol relative to that evoked by forskolin was found to be proportional to the number of receptors per cell. The number of receptors thus seems to determine the proportion of the inherent adenylate cyclase that can be activated by a beta-adrenergic agent. The levels of adenylate cyclase induced in membranes by GppNHp and by fluoride, relative to those induced by forskolin, were substantially higher with some cell lines than with others. These data and the results from WEHI-22 cells indicate that lymphoid cell lines differ in their content of functional C and N proteins.