The role of the cAMP-PKA system in the short-term regulation of striatal [¹⁴C]-2-deoxyglucose uptake in freely moving rats

The cyclic adenosine monophosphate (cAMP)-protein kinase (PK) A system has been shown to have stimulatory effects on glucose utilization in various tissues in vitro. However, little is known about the influence of cAMP on glucose utilization in vivo. In the present study, we examined how cAMP-related compounds affected [¹⁴C]-2-deoxyglucose (DG) uptake in the striatum of freely moving rats. An intrastriatal injection of dibutyryl-cyclic adenosine monophosphate (db-cAMP), although increasing local cerebral blood flow, was found to decrease the uptake of [¹⁴C]-2-DG in the striatum. This decrease of [¹⁴C]-2-DG uptake in the striatum was completely blocked by pretreatment with Rp-adenosine-3′,5′-cyclic monophosphorothioate triethylamine (Rp-cAMPS). Moreover, intrastriatal infusion of Rp-cAMPS alone produced a striking increase of [¹⁴C]-2-DG uptake in the striatum. These results strongly suggest that transient activation of the cAMP-PKA system can depress the glucose phosphorylation process of the rat brain in vivo.