Many excitable cells express a class of neurotransmitter receptors functionally defined by their ability to increase potassium conductance through G proteins of the Gi/G(o) class that directly activate the potassium channels. Biochemical studies have shown that these same receptors can also inhibit forskolin-stimulated adenylyl cyclase, although the functional significance of this effect remains unclear. In this study electrophysiological techniques were used to examine how activation of serotonin and gamma-aminobutyric acid receptors belonging to this class affect beta-adrenergic responses signaled through adenylyl cyclase. Surprisingly, activation of these receptors not only failed to inhibit but actually enhanced beta-adrenergic responses. These observations are consistent with evidence indicating that Gi-linked receptors can enhance the ability of Gs to stimulate certain adenylyl cyclases.