The ionic basis of adenosine receptor actions on post-ganglionic neurones in the rat.

AUTOR(ES)

Henon, B K

RESUMO

Adenosine inhibited three Ca2+-dependent potentials recorded intracellularly from post-ganglionic neurones of the rat superior cervical ganglion. A shoulder on the falling phase of the action potential elicited in normal Locke solution, a hyperpolarizing after-potential (h.a.p.) that follows the spike, and a regenerative Ca2+ spike elicited in Locke solution containing TTX and TEA were all reversibly inhibited by adenosine analogues in a dose-dependent fashion. The maximum rate of rise of the Ca2+ spike (dV/dt) was markedly reduced suggesting that the underlying mechanism of adenosine action is inhibition of the Ca2+ conductance mechanism and thus, the voltage-sensitive Ca2+ current. I/V curves in low Ca2+, high Mg2+, TTX, TEA, and Co2+ to block the Ca2+ current show no change in resistance in the presence of 2-chloroadenosine. The actions of adenosine were nearly eliminated in the presence of 1 mM-theophylline, an adenosine receptor antagonist. The order of agonist potency on the inhibition of the h.a.p. was: N-6-[L-phenylisopropyl] adenosine (L-PIA) greater than 2-chloroadenosine greater than adenosine greater than cyclic AMP = 5' AMP. The concentration of L-PIA which produced a half-maximal effect (EC50) was 0.5 microM and that for cyclic AMP was 100 microM. Dipyridamole, an adenosine uptake blocker, potentiated the effects of low concentrations of adenosine and shifted the dose-response curve for adenosine towards that of 2-chloroadenosine (EC50 = 1 microM). These results are consistent with the concept of an external adenosine receptor, but we are unable to assign a receptor subtype. Cyclic AMP mimicked the effects of adenosine, but these effects were eliminated by adenosine deaminase. Our results suggest that the electrogenic effects of bath-applied cyclic AMP may result from the metabolism of cyclic AMP to adenosine by ganglionic tissue. We conclude that adenosine activates a receptor on the neuronal cell surface to inhibit the voltage-dependent Ca2+ current.

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