Cafeína regula a captação de gaba e a sinalização de AMPc via receptores de adenosina

Caffeine is the most consumed psychostimulant drug in the world. Pharmacologically, caffeine acts as a non-selective antagonist of A1R and A2AR, which are widely expressed in retina layers. These adenosine receptors can modulate the GABAergic system, the principal inhibitory system of SNC, affecting its homeostasis, which could also affect cell differentiation, neuroprotection and other essential parameters during development. We accessed whether long-term caffeine exposure is able to modify GABA uptake in the avian retina and evaluated the mechanisms involved in this process. Chicken embryos aged E11 were offer a single injection of caffeine 30 mg/kg, in the air chamber. The animals were sacrificed, in E15, and the retina dissected for neurochemicals assays. Caffeine decreased GABA uptake only after 96h. Protein levels for A1R increased after caffeine treatment. There was a decrease in GABA uptake promoted by caffeine that was prevented by an acute treatment with H-89 (PKA inhibitor), CHA or CGS 21680 (A1R agonist and A2AR, respectively). Caffeine, after 96 hours of treatment, increased not only cAMP levels, but also, GAT-1 protein levels. Although the level of protein has increased to A1R, the mRNA is not modified by caffeine. These results support an idea that caffeine is a potential modulator of GABA transport during retinal development and that the PKA pathway plays an important role in the regulation of A1R function.