Tonic activation of A 2A adenosine receptors unmasks, and of A 1 receptors prevents, a facilitatory action of calcitonin gene-related peptide in the rat hippocampus (original) (raw)

2000, British Journal of Pharmacology

We investigated how manipulations of the degree of activation of adenosine A 1 and A 2A receptors in¯uences the action of the neuropeptide, calcitonin gene-related peptide (CGRP) on synaptic transmission in hippocampal slices. Field excitatory post-synaptic potentials (EPSPs) from the CA1 area were recorded. 2 When applied alone, CGRP (1 ± 30 nM) was without eect on ®eld EPSPs. However, CGRP (10 ± 30 nM) signi®cantly increased the ®eld EPSP slope when applied to hippocampal slices in the presence of the A 1 receptor antagonist, 1,3-dipropyl-8-cyclopenthyl xanthine (DPCPX, 10 nM), or in the presence of the A 2A adenosine receptor agonist CGS 21680 (10 nM). 3 The A 2A receptor antagonist, ZM 241385 (10 nM) as well as adenosine deaminase (ADA, 2 U ml 71), prevented the enhancement of ®eld EPSP slope caused by CGRP (30 nM) in the presence of DPCPX (10 nM), suggesting that this eect of CGRP requires the concomitant activation of A 2A adenosine receptors by endogenous adenosine. 4 The protein kinase-A inhibitors, N-(2-guanidinoethyl)-5-isoquinolinesulfonamide (HA-1004, 10 mM) and adenosine 3',5'-cyclic monophosphorothioate, Rp-isomer (Rp-cAMPS, 50 mM), as well as the inhibitor of ATP-sensitive potassium (K ATP) channels, glibenclamide (30 mM), prevented the facilitation of synaptic transmission caused by CGRP (30 nM) in the presence of DPCPX (10 nM), suggesting that this eect of CGRP involves both K ATP channels and protein kinase-A. 5 It is concluded that the ability of CGRP to facilitate synaptic transmission in the CA1 area of the hippocampus is under tight control by adenosine, with tonic A 1 receptor activation by endogenous adenosine`braking' the action of CGRP, and the A 2A receptors triggering this action.