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KMID : 0811719970010010001
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Korean Journal of Physiology & Pharmacology
1997 Volume.1 No. 1 p.1 ~ p.12
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The Role of Adenosine Receptors on Acetylcholine Release in the Rat Striatum
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Do Kyung Kim
Hyeon A Kim/Bong Kyu Choi/Do Kyung Kim/Hyeon A Kim/Bong Kyu Choi
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Abstract
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As it has been reported that the depolarization induced acetylcholine (ACh) release is modulated by activation of presynaptic A1 adenosine heteroreceptor and various evidence suggest that indicate the A2 adenosine receptor is present in the striatum, this study was undertaken to delineate the role of adenosine receptors on the striatal ACh release. Slices from the rat striatum were equilibrated with [3H]choline and then the release amount of the labelled product, [3H]ACh, which was evoked by electrical stimulation (rectangular pulses, 3 Hz, 2 ms, 24 mA, 5Vcm?1, 2 min), was measured, and the influence of various agents on the evoked tritium outflow was investigated. And also, quantitative receptor autoradiography and drug-receptor binding assay were performed in order to confirm the presence and characteristics of A1 and A2 adenosine receptors in the rat striatum. Adenosine (10sim100muM) and N6-cyclopentyladenosine (CPA, 1sim100muM) decreased the [3H]ACh release in a dose-dependent manner without changing the basal rate of release in the rat striatum. The reducing effects of ACh release by adenosine and CPA were abolished by 8-cyclopentyl-1,3-dipropy-Ixanthine (DPCPX, 2 muM), a selective A1, adenosine receptor antagonist, treatment. The effect of adenosine was potentiated markedly by 3,7-dimethyl-1-propargylxanthine (DMPX, 10 muM), a specific A2 adenosine receptor antagonist. 2-P-(2-carboxyethyl)phenethylamimo-5'-N- ethylcarboxamidoadenosine hydrochloride (CGS-21680C), in concentrations ranging from 0.01 to 10 muM, a recently introduced potent A2 adenosine receptor agonist, increased the [3H]ACh release in a dose related fashion without changing the basal rate of release. These effects were completely abolished by DMPX (10muM). In autoradiograrhy experiments, [3H]2-chloro-N6-cyclopentyladenosine ([3H] CCPA) bindings were highly localized in the hippocampus and the cerebral cortex. Additionally, lower levels of binding were found in the striatum. However, [3H]CGS-21680C bindings were highly localized in the striatal region with the greatest density of binding found in the caudate nucleus and putamen. Lower levels of binding were also found in the nucleus accumbens and olfactory tubercle. In drug-receptor binding assay, binding of [3H] CCPA to A1 adenosine receptors of rat striatal membranes was inhibited by CPA (Ki = 1.6 nM) and N-ethylcarboxamidoadenosine (NECA, Ki = 12.9 nM), but not by CGS-21680C (Ki = 2609.2 nM) and DMPX (Ki = 19,386 nM). In contrast, [3H]CGS-21680C binding to A2 denosine receptors was inhibited by CGS-21680C (Ki = 47.6 nM) and NECA (Ki = 44.9 nM), but not by CPA (Ki = 2099.2 nM) and DPCPX (Ki = 19,207 nM). The results presented here suggest that both types of A1 and A2 adenosine heteroreceptors exist and play an important role in ACh release in the rat striatal cholinergic neurons.
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KEYWORD
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Adenosine receptors, Acetylcholine, Striatum, Autoradiography,
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