A1 receptors self-regulate adenosine release in the striatum: evidence of autoreceptor characteristics

Adenosine A1 receptors are inhibitory G-protein coupled receptors that presynaptically regulate neurotransmitter release, but their role in self-regulating adenosine release is not known. In this study, we examined the modulation of evoked adenosine and dopamine efflux by A1 receptors and studied whether D1 receptors mediate these effects. Fast-scan cyclic voltammetry at carbon-fiber microelectrodes was used for the simultaneous detection of adenosine and dopamine efflux on a subsecond time scale. Short electrical stimulation trains delivered to the substantia nigra (60 pulses, 60 Hz) were used to evoke dopamine and adenosine release in the striatum. The adenosine A1 receptor agonist N6-cyclopentyladenosine (CPA, 1 mg/kg, i.p.) decreased both adenosine and dopamine efflux, although the effect for adenosine occurred more quickly than for dopamine. The A1 antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, 6 mg/kg, i.p.) increased stimulated adenosine release. The effects of CPA were partially attenuated by the dopamine D1 receptor antagonist SCH-23390. Thus, A1 and D1 receptors have a synergistic interaction that modulates both stimulated adenosine and dopamine. The decrease in adenosine is not a downstream effect of lowered dopamine release, as decreasing dopamine synthesis and release with α-methyl-p-tyrosine or increasing release with haloperidol had no effect on adenosine release. This study shows that A1 receptors have some characteristics of an autoreceptor, including self-regulation of adenosine release.

Graphical Abstract
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• Figure optionsDownload high-quality image (159 K)Download as PowerPoint slideResearch Highlights▶A1 receptors regulate adenosine release and have some properties of autoreceptors. ▶A1 receptors regulate dopamine release, but on a slower time scale. ▶Effects of A1 agonist are attenuated by a D1 antagonist.