Co-localized adenosine A1 and γ-aminobutyric acid B (GABA(B)) receptors of cerebellum may share a common adenylate cyclase catalytic unit

In synaptosomal membranes from rat cerebellum, additive responses to adenylate cyclase activity are observed between the beta adrenergic receptors present on the Purkinje cells and the adenosine A-1 receptors or γ-aminobutyric acid B (GABA(B)) receptors, which are both associated with the granule cells. In contrast, nonadditive responses are found with the activation of the adenosine A-1 and the GABA(B) receptors. Because both receptors are mainly associated with the same cell type, the nonadditive response indicates an interaction between the adenosine A-1, GABA(B) receptors and the adenylate cyclase. The present study suggests that the nonadditivity results from a limited number of adenylate cyclase catalytic units, which both receptor systems share. This conclusion was derived indirectly by showing that 1) a GABA(B) agonist did not affect the adenosine A-1 recognition site; 2) both receptors additively activated the high-affinity guanosine 5'-triphosphatase, which is believed to reflect the activation of the inhibitory guanine nucleotide unit; and 3) the nonadditivity was still observed after stimulation of adenylate cyclase activity with forskolin.