Adenosine modulates excitatory synaptic transmission and suppresses neuronal death induced by ischaemia in rat spinal motoneurones.
Although adenosine is an important neuromodulator, its role in modulating motor functions at the level of the spinal cord is poorly understood. In the present study, we investigated the effects of adenosine on excitatory synaptic transmission and neuronal death induced by experimental ischaemia by using whole-cell patch-clamp recordings from lamina IX neurones in spinal cord slices. Adenosine significantly decreased the frequency of miniature excitatory postsynaptic currents (mEPSCs) in almost all neurones examined that could be mimicked by an A(1) receptor agonist, N (6)-cyclopentyladenosine (CPA), and inhibited by an A(1) receptor antagonist, 8-cyclopentyl-1, 3-dipropylxanthine (DPCPX). Interestingly, adenosine increased mEPSC frequency in the presence of DPCPX in a subpopulation of neurones. In these neurones, an A(2A) receptor agonist, 2-[4-(2-carbonylethyl)-phenethylamino]-5'-N-ethylcarboxamidoadenosine (CGS21680), increased mEPSC frequency. Adenosine also induced an outward current that was blocked by the addition of Cs(+) and tetraethylammonium into the patch-pipette solution and inhibited in the presence of Ba(2+). The adenosine-induced outward current was mimicked by CPA, but not CGS21680, and inhibited by DPCPX. Moreover, superfusing with ischaemia simulating medium (ISM) generated an agonal inward current in all of the neurones tested. The latencies of the inward currents induced by ISM were significantly prolonged by adenosine or CPA, but not by CGS21680. These results suggest that adenosine receptors are functionally expressed in both the pre- and postsynaptic sites of lamina IX neurones and that their activation may exert multiple effects on motor function. Moreover, this study has provided a cellular basis for an involvement of A(1) receptors in the neuroprotective actions of adenosine.
Miyazaki
Nobuyuki
N
Department of Orthopaedic Surgery, Wakayama Medical University, 811-1 Kimiidera, Wakayama, 641-8510, Japan.
Nakatsuka
Terumasa
T
Takeda
Daisuke
D
Nohda
Kazuhiro
K
Inoue
Kazuhide
K
Yoshida
Munehito
M
D000241:Adenosine / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D016923:Cell Death; D019706:Excitatory Postsynaptic Potentials; D066298:In Vitro Techniques; D008159:Lumbar Vertebrae; D055369:Miniature Postsynaptic Potentials; D009046:Motor Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D018408:Patch-Clamp Techniques; D010627:Phenethylamines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043682:Receptor, Adenosine A1 / Q000378:metabolism; D043705:Receptor, Adenosine A2A / Q000378:metabolism; D017661:Receptors, Presynaptic / Q000187:drug effects / Q000378:metabolism*; D018047:Receptors, Purinergic P1 / Q000187:drug effects / Q000378:metabolism*; D012447:Sacrum; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D020760:Spinal Cord Ischemia / Q000378:metabolism* / Q000473:pathology; D009435:Synaptic Transmission / Q000187:drug effects; D014970:Xanthines / Q000494:pharmacology
D010627:Phenethylamines; D043682:Receptor, Adenosine A1; D043705:Receptor, Adenosine A2A; D017661:Receptors, Presynaptic; D018047:Receptors, Purinergic P1; D014970:Xanthines; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; C048599:N(6)-cyclopentyladenosine; C051360:1,3-dipropyl-8-cyclopentylxanthine; D000241:Adenosine