omega-agatoxin-iva and 3-7-dimethyl-1-propargylxanthine

Adenosine has been shown to increase the release of neurotransmitters by stimulation of adenosine A2 receptors. This effect probably depends on Ca2+ entry into presynaptic nerve terminals. In the present work the ability of the mixed adenosine A1/A2 agonist, 2-chloroadenosine, to stimulate Ca2+ uptake into rat brain synaptosomes was investigated. 45Ca2+ uptake was induced by 20 microM veratridine. In the absence of other drugs, 2-chloroadenosine (1 microM) decreased 45Ca2+ uptake into synaptosomes. Blocking the adenosine A1 receptor with 100 nM of 1,3-dipropyl-8-cyclopentylxanthine (DPCPX), 2-chloroadenosine (1 microM) increased rather than decreased the uptake of 45Ca2+ 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 microM; methoxyverapamil 1-10 microM) or N-type (omega-conotoxin GVIA, 500 nM) Ca2+ channel antagonists. The adenosine A2A selective agonist 2-p-(2-carboxyethyl)-phenethylamino-5'-N-ethyl-carboxamido-adenosi ne (CGS 21680), did not significantly modify Ca2+ uptake induced by veratridine. In contrast, the selective adenosine A2 receptor agonist, N6-(2-(3,5-dimethoxyphenyl)-2-(2-methylphenyl)ethyl)-adenosine (DPMA), in concentrations ranging from 10 nM to 1 microM increased Ca2+ uptake induced by veratridine. The selective adenosine A2 receptor antagonist 3,7-dimethyl-1-propargylxanthine (DMPX) at a concentration of 10 microM antagonized the stimulatory effect of DPMA (0.1 microM) on 45Ca2+ uptake. In conclusion, activation of adenosine A2 receptors increases Ca2+ uptake by synaptosomes depolarized by veratridine, which could explain the increase of neurotransmitter release observed when A2 receptors are activated.

Topics: 2-Chloroadenosine; Animals; Brain; Calcium Channel Blockers; Calcium Isotopes; Male; omega-Agatoxin IVA; Purinergic P1 Receptor Agonists; Rats; Rats, Wistar; Receptors, Purinergic P1; Spider Venoms; Synaptosomes; Theobromine