• Biomolecules & Therapeutics
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• 제12권2호
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• pp.68-73
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• 2004

This study was performed to investigate the regulatory mechanism of cerebral blood How of adenosine $A_2$ receptor agonist in the rats, and to define whether its mechanism is mediated by nitric oxide (NO), adenylate cyclase and guanylate cyclase. In pentobarbital-anesthetized, pancuronium-paralyzed and artificially ventilated male Sprague-Dawley rats, all drugs were applied topically to the cerebral cortex. Blood flow from cerebal cortex was measured using laser-Doppler flowmetry. Topical application of an adenosine $A_2$ receptor agonist [5'-(N-cyclopropyl)-carboxamidoadenosine (CPCA; 4 umol/l)] increased cerebral blood flow. This effect of CPCA (4 umol/l) was blocked by pretreatment with NO synthase inhibitor [$N^G$-nitro-L-argine methylester (L-NAME; 140 umol/l)] and adenylate cyclase inhibitor [MDL-12,330 (20 umol/l)]. But the effect of CPCA (4 umol/l) was not blocked by pretreatment with guanylate cyclase inhibitor [LY-83,583 (10 umol/l)]. These results suggest that adenosine $A_2$ receptor increases cerebral blood How. It seems that this action of adenosine $A_2$ receptor is mediated via the NO and the activation of adenylate cyclase in the cerebral cortex of the rats.

• Biomolecules & Therapeutics
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• 제13권3호
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• pp.138-142
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• 2005

Adenosine and GABA are known to be major inhitory neurotransmitters in the central nervous system and its receptors mediate various neurophamacological effects including cardiovascular modulatory effects. Inhibitory cardiovascular effects induced by intrathecal (i.t.) administration of adenosine $A_1$ receptor agonist and its modulation by cyclic AMP was suggested by our previous report. In this experiment, we examined the modulation of cardiovascular effects of adenosine $A_1$ receptor and adenosine $A_2$ receptor by $GABA_B$ receptors antagonist in the spinal cord. I.t. administration of 10 nmol of $N^6$-cyclohexyladenosine (CHA, an adenosine $A_1$ receptor agonist), I.t. administration of 2 nmol of 5'-(N-cyclopropyl)-carboxamidoadenosine (CPCA, an adenosine $A_2$ receptor agonist), pretreatment with 5-aminovaleric acid (a $GABA_B$ receptor antagonist, 50 nmol, i.t.) prior to administration of CHA and pretreatment with 5-aminovaleric acid (a $GABA_B$ receptor antagonist, 50 nmol, i.t.) prior to administration of CPCA were performed in anesthetized, artificially ventilated Sprague-Dawley rats. I.t. administration of 50 nmol of 5-aminovaleric acid significantly attenuated the inhibitory cardiovascular effects of CHA but did not attenuated the inhibitory cardiovascular effects of CPCA. It is suggested that cardiovascular responses of adenosine $A_1$ receptor is modulated by $GABA_B$ receptor and adenosine $A_2$ receptor is not modulated by $GABA_B$ receptor in the spinal cord.

• The Korean Journal of Physiology
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• 제30권1호
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• pp.85-96
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• 1996

Adenosine and its analogues are known to possess analgesic effects and to be involved in the opiate-induced antinociception as well. This study was designed to investigate the effects of three adenosine agonists, 5'- (N-cyclopropyl) -carboxamidoadenosine(CPCA), 5'-N-ethylcarboxamidoadeno-sine (NECA) and $N^6-cyclohexyladenosine$ (CHA) on the signal transmission in the spinal cord and also to elucidate mechanisms of their actions in the anesthetized cat. All the tested adenosine agonists(i.v,) exerted inhibitory effects on the responsiveness of the wide dynamic range (WDR) cells, the inhibitory action of CHA, an adenosine $A_1$ receptor agonist, $(80{\mu}g/Kg)$ being most weak. The intravenous CPCA, an adenosine $A_2$ receptor agonist, $(20{\mu}g\;/Kg)$ and NECA, nonspecific adenosine receptor agonist, $(20{\mu}g\;/Kg)$ inhibited the responses of WDR cells to pinch and C fiber stimulation more strongly than those to brush and A fiber stimulation. CPCA (i.v.) also suppressed the responses of WDR cells to thermal stimulus. And all the CPCA-induced inhibitions were caffeine-reversible. When CPCA was directly applied onto the spinal cord or intravenously administered into the spinal cat, on average, about three quarters of the CPCA-induced inhibitory effect was abolished. On the other hand, in the animal with spinal lesions in the ipsilateral dorsolateral area, the CPCA-induced inhibition was comparable to that observed in the spinal cats. In conclusion, this study shows that adenosine agonists strongly suppress the responses of WDR cells to pinch, C fiber stimulation and thermal stimuli mainly through the supraspinal adenosine $A_2-receptors$.

• 대한약리학회지
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• 제29권2호
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• pp.175-182
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• 1993

흰쥐 해마 (hippocampus)에서 acetylcholine(ACh) 유리에 미치는 adenosine 및 이에 미치는 magnesium의 역할에 관한 지견을 얻고자하여 $[^3H]-choline$으로 평형시킨 해마 slice를 사용하여 $[^3H]-ACh$ 유리에 미치는 여러가지 약물들의 영향을 관찰하였다. Adenosine $^*0.3{\sim}100{\mu}M$)은 전기자극 (3 Hz, $5\;Vcm^{-1}$, 2 ms, rectangular pulses)에 의한 $[^3H]-ACh$ 유리를 용량 의존적으로 감소시켰다. $A_1-adenosine$ 수용체 차단제인 8-cyclopentyl-1, 3-dipropylxanthine $(DPCPX,\;1-10\;{\mu}M)$은 용량 의존적으로 $[^3H]-ACh$ 유리를 증가시켰으며, adenosine과 $2{\mu}M$ DPCPX 동시 투여시 adenosine의 효과가 억제됨을 볼 수 있었다. $A_2$-수용체 흥분제인 5-(N-cyclopropyl)-carboxamidoadenosine $(CPCA,\;0.3{\sim}30\;{\mu}M)$은 자극에 의한 $[^3H]-ACh$ 유리를 용량 의존적으로 감소시켰으며, 이 역시 $2\;{\mu}M$ DPCPX 동시 투여시 그 효과가 차단됨을 관찰할 수 있었다. 그러나 또다른 $A_2$-흥분약인 CGS 21680C는 $[^3H]-ACh$ 유리에 별다른 영향을 미치지 못하였다. 한편 관류액내의 magnesium 농도를 변화시켰을때 magnesium 그 자체로는 $[^3H]-ACh$ 유리에 별다른 변화가 없었으며, magnesium을 4 mM로 증가시켰을때 adenosine의 효과가 크게 강화되어 용량 반응 곡선이 좌측으로 이동됨을 볼 수 있었다. 이상의 실험 결과로 adenosine은 흰쥐 해마의 choline 작동성 신경에 presynaptic $A_1-adenosine$ heteroreceptor를 통하여 ACh 유리 감소를 일으키며, 이러한 adenosine 작용은 magnesium이온에 의존적임을 알 수 있었다.