Drug-receptor-related stereoselectivities in fat cells

Abstract

In fat cells, with the aid of stereoisomers of norepinephrine, a correlation between the initial events in the drug-receptor interactions and the end pharmacologic effect was sought. In the presence of theophylline, the isomeric activity difference for the rise in intracellular cyclic AMP was 2.5 log units. The rise presumably occurs through the stereoselective interaction of the isomers at the β-adrenergic receptor and/or adenylate cyclase. The isomeric activity difference for the lipolysis, an end pharmacologic effect, was the same, 2.5 log units. Although the stereoselective rise in cyclic AMP indicates that the event preceding the rise must also be stereoselective, the incubation of (−)- or (+)-norepinephrine with (−)- 3H-norepinephrine with fat cell membrane particles failed to show the selectivity in binding. The methodological problems for such failure are discussed.