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小鼠和大鼠输精管中去甲肾上腺素释放的接头前调节:P1和P2嘌呤受体的作用

Prejunctional modulation of noradrenaline release in mouse and rat vas deferens: contribution of P1- and P2-purinoceptors.

作者信息

Kurz K, von Kügelgen I, Starke K

机构信息

Pharmakologisches Institut, Freiburg, Germany.

出版信息

Br J Pharmacol. 1993 Dec;110(4):1465-72. doi: 10.1111/j.1476-5381.1993.tb13986.x.

Abstract
  1. Prejunctional purinoceptors modulating the release of noradrenaline were compared in mouse and rat vas deferens. Tissue slices were preincubated with [3H]-noradrenaline and then superfused and stimulated electrically, in most experiments by trains of 60 pulses, 1 Hz. 2. In mouse vas deferens, 2-chloroadenosine (IC50 0.24 microM), beta,gamma-methylene-ATP (IC50 3.8 microM), alpha,beta-methylene-ATP (IC50 2.9 microM) and 2-methylthio-ATP (only 30 microM tested) reduced the evoked overflow of tritium. 8-Cyclopentyl-1,3-dipropylxanthine (DPCPX), 10 nM, antagonized the effect of 2-chloro-adenosine (apparent pKB 10.2) as well as of beta,gamma-methylene-ATP (apparent pKB 9.6) and alpha,beta-methylene-ATP. Suramin, 300 microM, attenuated the effect of 2-chloroadenosine at best very slightly, antagonized the effect of beta,gamma-methylene-ATP (apparent pKB 4.5) and, when combined with DPCPX 10 nM, caused a further marked shift to the right of the concentration-response curve of beta,gamma-methylene-ATP beyond the shift produced by DPCPX alone. 3. In rat vas deferens, 2-chloroadenosine (IC50 0.20 microM), beta,gamma-methylene-ATP (IC50 4.8 microM), alpha,beta-methylene-ATP (IC50 3.0 microM) and 2-methylthio-ATP (only 30 microM tested) also reduced the evoked overflow of tritium. DPCPX, 10 nM, antagonized the effect of 2-chloroadenosine (apparent pKB 9.7) as well as of beta,gamma-methylene-ATP (apparent pKB 9.6) and alpha,beta-methylene-ATP. Suramin, 300 microM, did not change the effect of 2-chloroadenosine, attenuated the effect of beta,gamma-methylene-ATP at best very slightly and, when combined with DPCPX, caused at best a very small shift to the right of the concentration-response curve of beta,gamma-methylene-ATP beyond the shift produced by DPCPX alone.4. It is concluded that prejunctional purinoceptor mechanisms in mouse and rat vas deferens are similar. In either species, both nucleosides such as adenosine and nucleotides such as beta,gamma-methylene-ATP activate a common release-inhibiting receptor which is a Pl- or, more specifically, A1-purinoceptor.There seems to be no need to postulate the existence of a novel prejunctional P3-purinoceptor.Moreover, the sympathetic terminal axons possess an additional P2-purinoceptor in both species which is activated by some nucleotides such as beta,gamma-methylene-ATP and 2-methylthio-ATP, although the activation of the P2-purinoceptor by beta,gamma-methylene-ATP is difficult to demonstrate in the rat.
摘要
  1. 对小鼠和大鼠输精管中调节去甲肾上腺素释放的接头前嘌呤受体进行了比较。组织切片先用[3H] - 去甲肾上腺素预孵育,然后进行灌流并电刺激,在大多数实验中采用1 Hz的60个脉冲串刺激。

  2. 在小鼠输精管中,2 - 氯腺苷(IC50 0.24 microM)、β,γ - 亚甲基 - ATP(IC50 3.8 microM)、α,β - 亚甲基 - ATP(IC50 2.9 microM)和2 - 甲硫基 - ATP(仅测试了30 microM)减少了诱发的氚溢出。10 nM的8 - 环戊基 - 1,3 - 二丙基黄嘌呤(DPCPX)拮抗2 - 氯腺苷(表观pKB 10.2)以及β,γ - 亚甲基 - ATP(表观pKB 9.6)和α,β - 亚甲基 - ATP的作用。300 microM的苏拉明对2 - 氯腺苷的作用至多仅有非常轻微的减弱,拮抗β,γ - 亚甲基 - ATP的作用(表观pKB 4.5),并且当与10 nM的DPCPX联合使用时,使β,γ - 亚甲基 - ATP的浓度 - 反应曲线进一步显著右移,超出单独使用DPCPX所产生的右移。

  3. 在大鼠输精管中,2 - 氯腺苷(IC50 0.20 microM)、β,γ - 亚甲基 - ATP(IC50 4.8 microM)、α,β - 亚甲基 - ATP(IC50 3.0 microM)和2 - 甲硫基 - ATP(仅测试了30 microM)也减少了诱发的氚溢出。10 nM的DPCPX拮抗2 - 氯腺苷(表观pKB 9.7)以及β,γ - 亚甲基 - ATP(表观pKB 9.6)和α,β - 亚甲基 - ATP的作用。300 microM的苏拉明不改变2 - 氯腺苷的作用,对β,γ - 亚甲基 - ATP的作用至多仅有非常轻微的减弱,并且当与DPCPX联合使用时,使β,γ - 亚甲基 - ATP的浓度 - 反应曲线至多仅有非常小的右移,超出单独使用DPCPX所产生的右移。

  4. 得出的结论是,小鼠和大鼠输精管中的接头前嘌呤受体机制相似。在这两个物种中,腺苷等核苷和β,γ - 亚甲基 - ATP等核苷酸都激活一种共同的释放抑制受体,该受体是P1 - 或更具体地说是A1 - 嘌呤受体。似乎没有必要假定存在一种新型的接头前P3 - 嘌呤受体。此外,交感神经末梢轴突在这两个物种中都具有一种额外的P2 - 嘌呤受体,该受体可被β,γ - 亚甲基 - ATP和2 - 甲硫基 - ATP等一些核苷酸激活,尽管在大鼠中很难证明β,γ - 亚甲基 - ATP对P2 - 嘌呤受体的激活作用。

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