Effects of guanine nucleotides on adenosine and glutamate modulation of cAMP levels in optic tectum slices from chicks.

Glutamate and adenosine both modulate adenylyl cyclase activity through interaction of their specific receptors with stimulatory or inhibitory G-proteins. Guanine nucleotides (GN), which modulate G-protein activity intracellularly, are also involved in the inhibition of glutamate responses, acting from the outside of the cells. We had previously reported that glutamate inhibits adenosine-induced cyclic AMP (cAMP) accumulation in slices obtained from the optic tectum of chicks. In the present study we investigated the interaction of GN with these two neurotransmitters and found that GN inhibit the inhibitory effect of glutamate on adenosine-induced cAMP accumulation and potentiate adenosine-induced cAMP accumulation. These effects were observed with 5'-guanylylimidodiphosphate (GppNHp) or GMP, but not with guanosine (the nucleoside). Besides, these interactions of GN occur via a metabotropic glutamate receptor (mGluR) sensitive to (1 S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (1 S,3R-ACPD) but not to L-2-amino-4-phosphonobutyrate (L-AP4). These effects were partially modulated by a mGluR antagonist, (RS)-alpha-methyl-4-carboxyphenylglycine ((RS)M-CPG), and by an adenosine receptor antagonist, 8-phenyltheophylline. GN only potentiated the adenosine response when adenosine was acting through its receptor positively linked to adenylyl cyclase. Therefore, the data show that guanine nucleotides not only inhibit glutamate-induced responses, but also stimulate adenosine-induced responses, a fact that may contribute to the understanding of the physiological functions of guanine nucleotides.