DECREASED BETA-2-ADRENERGIC RECEPTOR MESSENGER-RNA EXPRESSION IN RECEPTOR-DEFICIENT S49-LYMPHOMA CELLS

Many variants of the S49 mouse lymphoma cell have been isolated along the pathway of cyclic AMP generation and response. Two such variants, beta(p) and beta(d), were isolated by Johnson and colleagues and descr ibed in 1979 [Mol. Pharmacol. 15:16-27 (1979)]. The beta(p) and beta(d ) Variants express one half and one quarter, respectively, of the wild -type number of beta-2-adrenergic receptors. This observation has now been extended through the use of DNA-excess solution hybridization. Us ing this exquisitely sensitive technique for quantitation of gene and mRNA, we have been able to demonstrate that the beta-2-adrenergic rece ptor-deficient variant cells contain the same quantity of the beta-2-a drenergic receptor gene as the wild-type cells. In contrast, the beta- 2-adrenergic receptor-deficient variant cells express reduced quantiti es of beta-2-adrenergic receptor-specific mRNA. The amount of beta-2-a drenergic receptor-specific mRNA correlates very well with the reducti on in receptor expression in these cells. Both gene and mRNA in the wi ld-type and variant cells appear to be the same size, as judged by Sou thern and Northern analysis. Thus, the diminution of beta-2-adrenergic receptors in the beta(p) and beta(d) variants appears to reflect prim arily the relative paucity of gene transcripts in the variant cells. T hese data imply that variations in cellular content of beta-2-adrenerg ic receptor mRNA, which may occur among closely related cells, is one explanation for differences in receptor number.