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Inhibition by adenosine receptor agonists of synaptic transmission in rat periaqueductal grey neurons
Author(s) -
Bagley Elena E.,
Vaughan Christopher W.,
Christie MacDonald J.
Publication year - 1999
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.1999.219aa.x
Subject(s) - ccpa , agonist , neurotransmission , adenosine , adenosine a1 receptor , inhibitory postsynaptic potential , chemistry , excitatory postsynaptic potential , glutamatergic , pharmacology , biology , neuroscience , adenosine receptor , receptor , biochemistry , glutamate receptor
1 The actions of selective adenosine A 1 and A 2 receptor agonists were examined on synaptic currents in periaqueductal grey (PAG) neurons using patch‐clamp recordings in brain slices. 2 The A 1 receptor agonist 2‐chloro‐ N‐ cyclopentyladenosine (CCPA), but not the A 2 agonist, 2‐ p‐ (2‐carboxyethyl)phenethylamino‐5′‐ N‐ ethylcarboxamidoadenosine (CGS21680), inhibited both electrically evoked inhibitory (eIPSCs) 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 sufficient to inhibit synaptic transmission in the PAG. 4 CCPA decreased the frequency of spontaneous miniature action potential‐independent IPSCs (mIPSCs) but had no effect on their amplitude distributions. Inhibition persisted in nominally Ca 2+ ‐free, high Mg 2+ solutions and in 4‐aminopyridine. 5 The CCPA‐induced decrease in mIPSC frequency was partially blocked by the non‐selective protein kinase inhibitor staurosporine, the specific protein kinase A inhibitor 8‐para‐chlorophenylthioadenosine‐3′,5′‐cyclic monophosphorothioate (Rp‐8‐CPT‐cAMPS), and by 8‐bromoadenosine cyclic 3′,5′ monophosphate (8‐Br‐cAMP). 6 These results suggest that A 1 adenosine receptor agonists inhibit both GABAergic and glutamatergic synaptic transmission in the PAG. Inhibition of GABAergic transmission is mediated by presynaptic mechanisms that partly involve protein kinase A.