Inhibition of N-,P/Q- and other types of Ca2+ channels in rat hippocampal nerve terminals by the adenosine A1 receptor.
The effects of the adenosine A1 receptor agonist, N6-cyclopentyladenosine (CPA), on both the increase in intracellular free Ca2+ concentration ([Ca2+]i) and on the release of endogenous glutamate in rat hippocampal synaptosomes were studied. The inhibitory effect of CPA on the increase in [Ca2+]i stimulated with 4-aminopyridine was neutralized by the adenosine A1 receptor antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX). The inhibitory effect of CPA was greater in synaptosomes from the CA1 subregion than in whole hippocampal synaptosomes. The inhibitory effects of both CPA and of the Ca2+ channel blockers, omega-conotoxin GVIA, omega-conotoxin MVIIC or omega-conotoxin GVIA plus omega-conotoxin MVIIC, were greater than those caused by the Ca2+ channel blockers. The release of endogenous glutamate was inhibited by 41% by CPA. The inhibition observed when CPA and omega-conotoxin GVIA or CPA and omega-conotoxin MVIIC were present was also greater than the inhibition by the Ca2+ channel blockers alone. The presence of both omega-conotoxin GVIA and omega-conotoxin MVIIC did not completely inhibit the release of glutamate, and CPA significantly enhanced this inhibition. The membrane potential and the accumulation of [3H]tetraphenylphosphonium of polarized or depolarized synaptosomes was not affected by CPA, suggesting that adenosine did not increase potassium conductances. The present results suggest that, in hippocampal glutamatergic nerve terminals, adenosine A1 receptor activation partly inhibits P/Q- and other non-identified types of Ca2+ channels.
Ambrósio
A F
AF
Center for Neuroscience of Coimbra, Department of Zoology and Faculty of Medicine, University of Coimbra, Portugal.
Malva
J O
JO
Carvalho
A P
AP
Carvalho
C M
CM
D000227:Adenine Nucleotides / Q000378:metabolism; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004566:Electrodes; D005089:Exocytosis / Q000187:drug effects; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009411:Nerve Endings / Q000187:drug effects / Q000378:metabolism*; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D051381:Rats; D017208:Rats, Wistar; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism
D000227:Adenine Nucleotides; D002121:Calcium Channel Blockers; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D018698:Glutamic Acid