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The Role of Adenosine Receptors on Acetylcholine Release in the Rat Striatum

Kim, Do-Kyung   (Department of Pharmacology, Wonkwang University School of Medicine and Medicinal Resources Research Center of Wonkwang UniversityUU0001021  ); Kim, Hyeon-A   (Department of Pharmacology, Wonkwang University School of Medicine and Medicinal Resources Research Center of Wonkwang UniversityUU0001021  ); Choi, Bong-Kyu   (Department of Pharmacology, Wonkwang University School of Medicine and Medicinal Resources Research Center of Wonkwang UniversityUU0001021  );
  • 초록

    As it has been reported that the depolarization induced acetylcholine (ACh) release is modulated by activation of presynaptic $A_1$ adenosine heteroreceptor and various evidence suggest that indicate the $A_2$ 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, $5\;Vcm^{-1}$ , 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 $A_1$ and $A_2$ adenosine receptors in the rat striatum. Adenosine $(10{sim}100\;{mu}M)$ and $N^6$ -cyclopentyladenosine (CPA, $1{sim}100\;{mu}M)$ 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 ${mu}M$ ), a selective $A_1$ , adenosine receptor antagonist, treatment. The effect of adenosine was potentiated markedly by 3,7-dimethyl-1-propargylxanthine (DMPX, 10 ${mu}M$ ), a specific $A_2$ adenosine receptor antagonist. 2-P-(2-carboxyethyl)phenethylamimo-5'-N- ethylcarboxamidoadenosine hydrochloride (CGS-21680C), in concentrations ranging from 0.01 to 10 ${mu}M$ , a recently introduced potent $A_2$ 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 $(10\;{mu}M)$ . In autoradiograrhy experiments, $[^3H]$ 2-chloro- $N^6$ -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 $A_1$ adenosine receptors of rat striatal membranes was inhibited by CPA ( $K_i$ = 1.6 1.6 nM) and N-ethylcarboxamidoadenosine (NECA, $K_i$ = 12. 12.9 nM), but not by CGS-21680C ( $K_i$ = 260 2609.2 nM) and DMPX ( $K_i$ = 19, 19,386 nM). In contrast, $[^3H]$ CGS-21680C binding to $A_2$ denosine receptors was inhibited by CGS-21680C ( $K_i$ = 47. 47.6 nM) and NECA ( $K_i$ = 44. 44.9 nM), but not by CPA ( $K_i$ = 209 2099.2 nM) and DPCPX ( $K_i$ = 19, 19,207 nM). The results presented here suggest that both types of $A_1$ and $A_2$ adenosine heteroreceptors exist and play an important role in ACh release in the rat striatal cholinergic neurons.


  • 주제어

    Adenosine receptors .   Acetylcholine .   Striatum .   Autoradiography.  

 저자의 다른 논문

  • Choi, Bong-Kyu (24)

    1. 1991 "가토 해마에서 Acetylcholine 유리에 미치는 Oxotremorine 및 Forskolin의 영향" The Korean journal of pharmacology : official journal of the Society of Pharmacology, Republic of Korea 27 (2): 89~97    
    2. 1992 "흰쥐 해마에서 Acetylcholine 유리에 미치는 $N^6-Cyclopentyladenosine$ 및 Forskolin의 영향" The Korean journal of pharmacology : official journal of the Society of Pharmacology, Republic of Korea 28 (2): 129~136    
    3. 1992 "몇가지 중금속이 배양 섬유모세포에 미치는 세포독성에 관한 연구" 한국독성학회지 = The Korean journal of toxicology 8 (1): 119~129    
    4. 1993 "흰쥐 해마에서 Acetylcholine 유리에 미치는 Adenosine 및 Magnesium의 영향" The Korean journal of pharmacology : official journal of the Society of Pharmacology, Republic of Korea 29 (2): 175~182    
    5. 1994 "흰쥐 해마에서 Acetylcholine 유리에 미치는 Adenosine 수용체의 역할" The Korean journal of pharmacology : official journal of the Society of Pharmacology, Republic of Korea 30 (2): 145~152    
    6. 1994 "흰쥐 해마에서 Acetylcholine 유리에 관여하는 Adenosine Receptor의 Post-Receptor 기전에 관한 연구" The Korean journal of pharmacology : official journal of the Society of Pharmacology, Republic of Korea 30 (3): 263~272    
    7. 1995 "흰쥐 해마에서 Norepinephrine 유리에 미치는 Protein Kinase C 의 영향" The Korean journal of pharmacology : official journal of the Society of Pharmacology, Republic of Korea 31 (2): 145~152    
    8. 1996 "흰쥐 해마에서 Norepinephrine 유리에 미치는 Adenosine Receptor의 Post-Receptor 기전에 관한 연구" The Korean journal of pharmacology : official journal of the Society of Pharmacology, Republic of Korea 32 (1): 1~11    
    9. 1996 "허혈이 유발된 흰쥐 해마에서 Acetylcholine 유리에 미치는 Adenosine 수용체의 역할" The Korean journal of pharmacology : official journal of the Society of Pharmacology, Republic of Korea 32 (2): 127~138    
    10. 1996 "허혈이 유발된 흰쥐 해마에서 Norepinephrine 유리에 미치는 Adenosine 수용체의 역할" The Korean journal of pharmacology : official journal of the Society of Pharmacology, Republic of Korea 32 (2): 139~150    

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