Pharmacological Survey of Medicinal Plants for Activity at Dopamine Receptor Subtypes. I. Activation of D1-Like Receptor Linked Adenylyl Cyclase

Abstract

Nearly 100 aqueous, organic and alcoholic extracts of 46 Bolivian, Chinese and Indian medicinal plants were evaluated for their ability to stimulate adenylyl cyclase using Sf9 cells expressing rat D1a dopamine receptors in a broken cell assay. The aqueous extract of Cestrum parqui, a Bolivian plant of the Solanaceae, stimulated adenylyl cyclase in Sf9 cells expressing either rat D1a or rat D1b receptors, but no stimulation was observed in uninfected Sf9 cells. Flupenthixol, a nonselective dopaminergic antagonist, was found to attenuate both dopamine- and extract-dependent stimulation of adenylyl cyclase. The extract stimulated adenylyl cyclase in a concentration-dependent manner. However, adenylyl cyclase activity returned to basal levels at the highest concentration of extract that was tested. The extract was also evaluated for the ability to stimulate adenylyl cyclase in stably transfected HEK cells expressing human D1 receptors using a cAMP accumulation, whole cell assay. The extract stimulated HEK cells expressing human D1a dopamine receptors, but no enzyme stimulation was observed in untransfected HEK cells. Studies using transfected HEK cells expressing D2 receptors indicate that this extract also has intrinsic activity at D2 dopamine receptor. These studies suggest that this plant extract contains a component that is an agonist at dopamine receptors.