Adenosine A(2) receptor activation facilitates Ca-45(2+) uptake by rat brain synaptosomes

Adenosine has been shown to increase the release of neurotransmitters by stimulation of adenosine A(2) receptors. This effect probably depends on Ca2+ entry into presynaptic nerve terminals. In the present work the ability of the mixed adenosine A(1)/A(2) agonist, 2-chloroadenosine, to stimulate Ca2+ uptake into rat brain synaptosomes was investigated. Ca-45(2+) uptake was induced by 20 mu M veratridine. In the absence of other drugs, 2-chloroadenosine (1 mu M) decreased Ca-45(2+) uptake into synaptosomes. Blocking the adenosine A(1) receptor with 100 nM of 1,3-dipropyl-8-cyclopentylxanthine (DPCPX), 2-chloroadenosine (1 mu M) increased rather than decreased the uptake of Ca-45(2+) into synaptosomes. The excitatory effect of 2-chloroadenosine observed in the presence of DPCPX was reversed by 200 nM of omega-agatoxin-IVA, a specific P-type Ca2+ channel antagonist, but not by L-type (nifedipine, 100 nM to 1 mu M; methoxyverapamil 1-10 mu M) or N-type (omega-conotoxin GVIA, 500 nM) Ca2+ channel antagonists. The adenosine A(2A) selective agonist, 2-p-(2-carboxy-ethyl)-phenethylamino-5'-N-ethyl-carboxamido-adenosine (CGS 21680), did not significantly modify Ca2+ uptake induced by veratridine. In contrast, the selective adenosine A(2) receptor agonist, N-6-(2-(3,5-dimethoxyphenyl)-2-(2-methylphenyl)ethyl)-adenosine (DPMA), in concentrations ranging from 10 nM to 1 mu M increased Ca2+ uptake induced by veratridine. The selective adenosine A(2) receptor antagonist 3,7-dimethyl-1-propargylxanthine (DMPX) at a concentration of 10 mu M antagonized the stimulatory effect of DPMA (0.1 mu M) on Ca-45(2+) uptake. In conclusion, activation of adenosine A(2) receptors increases Ca2+ uptake by synaptosomes depolarized by veratridine, which could explain the increase of neurotransmitter release observed when A(2) receptors are activated.