Inhibition of striatal GABA release by the adenosine A2a receptor is not mediated by increases in cyclic AMP.
The adenosine A2a receptor inhibition of potassium (15 mM)-evoked GABA release from striatal nerve terminals has been examined. High extracellular calcium concentrations (4 mM) reduced the effect of the A2a receptor agonist CGS-21680 (1 nM). CGS-21680 inhibited GABA release in the presence of the L-type calcium channel blocker nifedipine, which itself inhibited evoked GABA release (by 16 +/- 4%). omega-Conotoxin inhibited the evoked release by 45 +/- 4% and prevented the action of CGS-21680. Forskolin and 8-bromo cyclic AMP both stimulated evoked GABA release at low concentrations, but at higher concentrations they abolished the inhibition by CGS-21680 without affecting the evoked release. The nonselective protein kinase inhibitor H-7 inhibited both the evoked release and the inhibition by CGS-21680, whereas the selective protein kinase A and G inhibitor HA-1004 had no effect on either evoked release or the action of CGS-21680. Pretreatment with pertussis toxin did not affect the A2a receptor-mediated inhibition. Therefore, the effect of A2a receptor stimulation was not mediated by protein kinases A or G but was inhibited by elevated cyclic AMP levels and mimicked by inhibitors of the N-type calcium channel and protein kinase C.
Kirk
I P
IP
Department of Pharmacology, University of Cambridge, England.
Richardson
P J
PJ
D000818:Animals; D002118:Calcium / Q000502:physiology; D003342:Corpus Striatum / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism* / Q000502:physiology; D005260:Female; D018756:GABA Antagonists; D008297:Male; D037342:Pertussis Toxin; D011494:Protein Kinases / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018047:Receptors, Purinergic P1 / Q000502:physiology*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D018756:GABA Antagonists; D018047:Receptors, Purinergic P1; D010566:Virulence Factors, Bordetella; D005680:gamma-Aminobutyric Acid; D000242:Cyclic AMP; D037342:Pertussis Toxin; D011494:Protein Kinases; D002118:Calcium