Expression of genes for metabolism of cyclic adenosine 3',5' monophosphate in somatic cells. II. The effects of prostaglandin E₁ and theophylline on parental and hybrid cells

Clonal differences in the response to prostaglandin E₁ (PGE₁) were found when changes in the intracellular concentration of cyclic adenosine 3':5' monophosphate (cyclic AMP) were measured following exposure to this agent in a variety of cell lines cultured in vitro. When PGE₁ responses were present, the effect was nearly maximal after a 5 min exposure and was well maintained for 60 min. Dose response curves for PGE₁ were complex and also exhibited clonal variation. The relative potencies of prostaglandins were: PGE₁ > PGE₂ > PGA₁. PGF(1α) and PGB₁ were inactive at the concentration tested, indicating receptor specificity. When parental lines with no or small responses to PGE₁ were fused to cells with larger responses to PGE₁, the resulting hybrid cells expressed high levels of PGE₁ responsiveness in the majority of cases. Clonal differences in potentiation by theophylline of peak PGE₁ or catecholamine effects on intracellular cyclic AMP levels were also found. When theophylline sensitive cells were fused to theophylline insensitive cells, the resulting hybrids were responsive to theophylline. Thus, the inheritance of PGE and theophylline responses in somatic cell hybrids is distinctly different from that seen for β adrenergic responses, suggesting fundamental differences in their genetic regulation. These data could indicate different types of receptor mechanisms for catecholamines and prostaglandins.