Functional adenosine al receptors in goldfish brain: Regional distribution and inhibition of K +-evoked glutamate release from cerebellar slices

Abstract

In goldfish brain, [ 3H]cyclohexyladenosine binding sites are ubiquitously distributed with a maximum in the hypothalamus and a minimum in the spinal cord. The binding parameters measured in cerebellar membranes ( K d = 0.88 ± 0.08nM; B max = 59.65 ± 2.62fmol/mg protein) are not significantly different from those of the whole brain. In perfused goldfish cerebellar slices, stimulation of cyclic AMP accumulation by 10 −5 M forskolin was markedly reduced (58.7%) by treatment with 10 −4 M cyclohexyl-adenosine, an adenosine Al receptor agonist, and the reduction was reversed in the presence of 10 −4 M 8-cyclopentyltheophylline, a selective Al receptor antagonist. In the same brain preparation, 30 mM K + stimulated the release of glutamate, glutamine, glycine and GABA in a Ca 2+-dependent manner, whereas the aspartate and taurine release was Ca 2+-independent. Cyclohexyladenosine inhibited the 30 mM K +-evoked release of glutamate in a dose-related manner. This effect was reversed by 8-cyclopentyltheophylline. These results support the hypothesis that adenosine A1 receptors present in goldfish cerebellum are involved in the modulation of glutamate transmitter release.