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

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Abstract
Adenosine inhibited 3 Ca2+-dependent potentials recorded intracellularly from post-ganglionic neurons of the rat superior cervical ganglion. A shoulder on the falling phase of the action potential elicited in normal Locke solution, a hyperpolarizing afterpotential (HAP) that follows the spike, and a regenerative Ca2+ spike elicited in Locke solution containing TTX [tetrodotoxin] and TEA [tetraethylammonium] 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 [current/voltage] 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 HAP was N-6-[L-phenylisopropyl] adenosine (L-PIA) > 2-chloroadenosine > adenosine > cAMP = 5'' AMP. The concentration of L-PIA which produced a half-maximal effect (EC50) was 0.5 .mu.M and that for cAMP was 100 .mu.M. 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 .mu.M). This is consistent with the concept of an external adenosine receptor, but a receptor subtype was unassignable. cAMP mimicked the effects of adenosine, but these effects were eliminated by adenosine deaminase. The electrogenic effects of bath-applied cAMP may result from the metabolism of cAMP to adenosine by ganglionic tissue. Adenosine activates a receptor on the neuronal cell surface to inhibit the voltage-dependent Ca2+ current.