British journal of pharmacology, 2002-05, Vol.136 (2), p.296-302
2002
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- Autor(en) / Beteiligte
- Titel
- Presynaptic adenosine A2A receptors enhance GABAergic synaptic transmission via a cyclic AMP dependent mechanism in the rat globus pallidus
- Ist Teil von
- British journal of pharmacology, 2002-05, Vol.136 (2), p.296-302
- Ort / Verlag
- Oxford, UK: Blackwell Publishing Ltd
- Erscheinungsjahr
- 2002
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- We previously reported a presynaptic facilitatory action of A2A receptors on GABAergic synaptic transmission in the rat globus pallidus (GP). In the present study we identify the intracellular signalling mechanisms responsible for this facilitatory action of A2A receptors, using biochemical and patch‐clamp methods in rat GP slices. The adenosine A2A receptor selective agonist CGS21680 (1, 10 μM) and the adenylyl cyclase activator forskolin (1, 10 μM) both significantly increased cyclic AMP accumulation in GP slices. The CGS21680 (1 μM)‐mediated increase in cyclic AMP was inhibited by the A2A receptor selective antagonist KF17837 (10 μM). In an analysis of miniature inhibitory postsynaptic currents (mIPSCs), forskolin (10 μM) increased the mIPSC frequency without affecting their amplitude distribution, a result similar to that previously reported with CGS21680. The adenylyl cyclase inhibitor 9‐(tetrahydro‐2‐furanyl)‐9H‐purin‐6‐amine (SQ22,536, 300 μM) abolished the CGS21680‐induced enhancement in the frequency of mIPSCs. H‐89 (10 μM), a selective inhibitor for cyclic AMP‐dependent protein kinase (PKA), blocked the CGS21680‐induced enhancement of the mIPSC frequency. The calcium channel blocker CdCl2 (100 μM) did not prevent CGS21680 from increasing the frequency of mIPSCs. These results indicate that A2A receptor‐mediated potentiation of mIPSCs in the GP involves the sequential activation of the A2A receptor, adenylyl cyclase, and then PKA, and that this facilitatory modulation could occur independently of presynaptic Ca2+ influx. British Journal of Pharmacology (2002) 136, 296–302; doi:10.1038/sj.bjp.0704702
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0007-1188eISSN: 1476-5381DOI: 10.1038/sj.bjp.0704702Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_1573342
- Format
- –
- Schlagworte
- Action Potentials - drug effects, Action Potentials - physiology, Adenosine A2A receptor, Animals, basal ganglia, Biological and medical sciences, brain slices, Central nervous system, Central neurotransmission. Neuromudulation. Pathways and receptors, CGS21680, Cyclic AMP - physiology, Fundamental and applied biological sciences. Psychology, GABAA IPSCs, gamma-Aminobutyric Acid - metabolism, gamma-Aminobutyric Acid - secretion, globus pallidus, Globus Pallidus - drug effects, Globus Pallidus - metabolism, In Vitro Techniques, KF17837, Male, Purinergic P1 Receptor Agonists, Rats, Rats, Sprague-Dawley, Receptor, Adenosine A2A, Receptors, Presynaptic - agonists, Receptors, Presynaptic - metabolism, Receptors, Purinergic P1 - metabolism, Synaptic Transmission - physiology, Vertebrates: nervous system and sense organs