Purinergic modulation of [(3)H]GABA release from rat hippocampal nerve terminals.
The hippocampal GABAergic system is assumed not to be a target for purine modulation. We have now confirmed that neither adenosine A(1) and A(3) receptor nor nucleotide P(2) or P(4) receptor activation modified the K(+)-evoked [(3)H]GABA release from hippocampal synaptosomes. However, activation of adenosine A(2A) receptors with CGS 21680 (10 nM) or HENECA (30 nM) facilitated GABA release by 32% and 21%, respectively. These effects were prevented by the A(2A) antagonist, ZM 241385 (20 nM). A(2A) receptors may activate adenylate cyclase and protein kinase A since CGS 21680 (10 nM) facilitation was partially prevented by 8-bromo-cAMP (1 mM), forskolin (10 microM) and HA-1004 (10 microM). Protein kinase C may also be recruited, since chelerythrine (6 microM) and phorbol-12, 13-didecanoate (250 nM) attenuated CGS 21680 (10 nM) facilitation of [(3)H]GABA release. Omega-agatoxin-IVA (200 nM) occluded CGS 21680 facilitation suggesting the involvement of P-type calcium channels. Thus, the adenosine A(2A) receptor system appears to be one of the first presynaptic neuromodulatory systems able to enhance the evoked release of GABA from hippocampal nerve terminals.
Cunha
R A
RA
University of Lisbon, Faculty of Medicine, Laboratory of Neurosciences, Av. Prof. Egas Moniz, 1649-028, Lisbon, Portugal. racunha@neurosciencias.pt
Ribeiro
J A
JA
D000241:Adenosine / Q000502:physiology; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020865:Calcium Channels, P-Type / Q000187:drug effects / Q000378:metabolism; D000242:Cyclic AMP / Q000502:physiology; D004558:Electric Stimulation; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D009411:Nerve Endings / Q000187:drug effects / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D043705:Receptor, Adenosine A2A; D043684:Receptor, Adenosine A3; D018047:Receptors, Purinergic P1 / Q000187:drug effects; D018048:Receptors, Purinergic P2 / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D002121:Calcium Channel Blockers; D020865:Calcium Channels, P-Type; D043705:Receptor, Adenosine A2A; D043684:Receptor, Adenosine A3; D018047:Receptors, Purinergic P1; D018048:Receptors, Purinergic P2; D005680:gamma-Aminobutyric Acid; D000242:Cyclic AMP; D011493:Protein Kinase C; D000241:Adenosine