Inhibition by adenosine receptor agonists of synaptic transmission in rat periaqueductal grey neurons

1. The actions of selective adenosine A(1) and A(2) receptor agonists were examined on synaptic currents in periaqueductal grey (PAG) neurons using pa tch-clamp recordings in brain slices. 2. The A(1) receptor agonist 2-chloro-N-cyclopentyladenosine (CCPA), but no t the A(2) agonist, 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamid oadenosine (CGS21680), inhibited both electrically evoked inhibitory (eIPSC s) and excitatory (eEPSCs) postsynaptic currents. The actions of CCPA were reversed by the A(1) receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX). 3. In the absence or presence of forskolin, DPCPX had no effect on eIPSCs, suggesting that concentrations of tonically released adenosine are not suff icient to inhibit synaptic transmission in the PAG. 4. CCPA decreased the frequency of spontaneous miniature action potential-i ndependent IPSCs (mIPSCs) but had no effect on their amplitude distribution s. Inhibition persisted in nominally Ca2+-free, high Mg2+ solutions and in 4-aminopyridine. 5. The CCPA-induced decrease in mIPSC frequency was partially blocked by th e non-selective protein kinase inhibitor staurosporine, the specific protei n kinase A inhibitor 8-para-chlorophenylthioadenosine-3',5'-cyclic monophos phorothioate (Rp-8-CPT-cAMPS), and by 8-bromoadenosine cyclic 3',5' monopho sphate (8-Br-cAMP). 6. These results suggest that A(1) adenosine receptor agonists inhibit both GABAergic and glutamatergic synaptic tr transmission in the PAG. Inhibitio n of GABAergic transmission is mediated by presynaptic mechanisms that part ly involve protein kinase A.