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猫结肠环行肌中由α1-肾上腺素能受体和P2-嘌呤能受体介导的收缩

Contractions mediated by alpha 1-adrenoceptors and P2-purinoceptors in a cat colon circular muscle.

作者信息

Venkova K, Milne A, Krier J

机构信息

Department of Physiology, Michigan State Univ., East Lansing 48823-1101.

出版信息

Br J Pharmacol. 1994 Aug;112(4):1237-43. doi: 10.1111/j.1476-5381.1994.tb13216.x.

Abstract
  1. The postjunctional excitatory and inhibitory effects of adrenoceptor and purinoceptor agonists and antagonists were studied in circular smooth muscle strips of cat colon. 2. In the presence of tetrodotoxin (0.5 microM), noradrenaline caused contraction or relaxation of circular smooth muscle at resting tension or with raised tone, respectively. The noradrenaline-evoked contractions were potentiated and the noradrenaline-evoked relaxations were antagonized by propranolol (1 microM), suggesting beta-adrenoceptor involvement. 3. At resting tension, noradrenaline, adrenaline and the selective alpha 1-adrenoceptor agonist, phenylephrine, caused concentration-dependent contractile responses, with EC50 values of 1.8 +/- 0.2 microM, 1.9 +/- 0.4 microM and 4.3 +/- 1.7 microM, respectively. The EC50 values and the amplitude of maximal responses were not significantly different from one another. Clonidine (0.1-500 microM), a selective alpha 2-adrenoceptor agonist, was not effective. 4. Prazosin (0.1-9 microM), competitively antagonized the contractile effects of noradrenaline with an estimated pA2 value of 6.93 and a slope of 1.07 +/- 0.03. The Kb values, estimated from a single shift (0.1 microM prazosin) of the concentration-response curves to noradrenaline, adrenaline and phenylephrine were 92.8 +/- 9.3 nM, 108.7 +/- 6.4 nM and 18.4 +/- 3.1 nM, respectively. 5. At resting tension, adenosine 5' triphosphate (ATP, 5-1000 microM), alpha,beta-methylene adenosine 5'-triphosphate (alpha,beta-MeATP, 0.05-50 microM), beta,gamma-methylene adenosine 5'-triphosphate (beta,gamma-MeATP, 0.5-100 microM), and 2-methylthioadenosine 5'-triphosphate (2-MeSATP, 1-500 microM) caused concentration-dependent contractions with EC50 values of 60.5 +/- 15.9 microM, 0.7 +/- 0.1 microM, 7.6 +/- 0.1 microM and 25.3 +/- 12.8 microM, respectively. The maximal responses to alpha, beta-MeATP and beta,gamma-MeATP were greater than maximal responses to 2-MeSATP and ATP.6. Suramin (50-500 microM), competitively antagonized the contractile responses of alpha,beta-MeATP with an estimated pA2 value of 4.92 and a slope of 1.08 +/- 0.04. The Kb values, estimated from a single shift(1I00 microM suramin) of the concentration-response curves to ATP, alpha,beta-MeATP, beta,gamma-MeATP and 2MeSATPwere 52.3 +/- 20.2 microM, 25.2 +/- 4.5 microM, 21.7 +/- 11.0 microM and 11.6 +/- 2.7 microM, respectively.7. At resting tension, reactive blue 2 (100 microM), a selective antagonist of the P2Y-purinoceptor, and 8-(p-sulphophenyl)-theophylline (8-SPT) (1 microM), a selective antagonist of the PI-purinoceptor, did not antagonize the contractile responses to alpha,beta-MeATP (0.5-5 microM). Contractile responses to ATP(50-500 microM) were not altered by 8-SPT (I microM) but were potentiated by reactive blue 2 (100 microM).8. With raised tone, ATP and 2-MeSATP caused a relaxant effect. This effect of ATP was not altered by either tetrodotoxin (TTX) (0.5 microM) or suramin (100 microM), but was antagonized by reactive blue 2(100 microM) and 8-SPT (1 microM), suggesting that inhibitory P2y- and P1-purinoceptors are involved. In contrast, alpha,beta-MeATP and Beta,gamma-MeATP caused only contractions. This contractile effect of alpha,beta-MeATPwas resistant to TTX (0.5 microM) and antagonized by suramin (100 microM).9. In summary, cat colon circular muscle contains postjunctional alpha 1-adrenoceptors and P2X purinoceptors which mediate contractions and P2y- and PI-purinoceptors which mediate relaxation.Postjunctional alpha2-adrenoceptors appear not to be present.
摘要
  1. 研究了肾上腺素能受体和嘌呤能受体激动剂及拮抗剂对猫结肠环形平滑肌条的节后兴奋和抑制作用。2. 在存在河豚毒素(0.5微摩尔/升)的情况下,去甲肾上腺素分别在静息张力或张力升高时引起环形平滑肌收缩或舒张。普萘洛尔(1微摩尔/升)增强了去甲肾上腺素引起的收缩,拮抗了去甲肾上腺素引起的舒张,提示有β肾上腺素能受体参与。3. 在静息张力下,去甲肾上腺素、肾上腺素和选择性α1肾上腺素能受体激动剂苯肾上腺素引起浓度依赖性收缩反应,其半数有效浓度(EC50)值分别为1.8±0.2微摩尔/升、1.9±0.4微摩尔/升和4.3±1.7微摩尔/升。EC50值和最大反应幅度彼此无显著差异。选择性α2肾上腺素能受体激动剂可乐定(0.1 - 500微摩尔/升)无效。4. 哌唑嗪(0.1 - 9微摩尔/升)竞争性拮抗去甲肾上腺素的收缩作用,估计pA2值为6.93,斜率为1.07±0.03。根据浓度 -反应曲线对去甲肾上腺素、肾上腺素和苯肾上腺素单次移动(0.1微摩尔/升哌唑嗪)估计的解离常数(Kb)值分别为92.8±9.3纳摩尔/升、108.7±6.4纳摩尔/升和18.4±3.1纳摩尔/升。5. 在静息张力下,5'-三磷酸腺苷(ATP,5 - 1000微摩尔/升)、α,β-亚甲基-5'-三磷酸腺苷(α,β-MeATP,0.05 - 50微摩尔/升)、β,γ-亚甲基-5'-三磷酸腺苷(β,γ-MeATP,0.5 - 100微摩尔/升)和2-甲硫基-5'-三磷酸腺苷(2-MeSATP,1 - 500微摩尔/升)引起浓度依赖性收缩,EC50值分别为60.5±15.9微摩尔/升、0.7±0.1微摩尔/升、7.6±0.1微摩尔/升和25.3±12.8微摩尔/升。对α,β-MeATP和β,γ-MeATP的最大反应大于对2-MeSATP和ATP的最大反应。6. 苏拉明(50 - 500微摩尔/升)竞争性拮抗α,β-MeATP的收缩反应,估计pA2值为4.92,斜率为1.08±0.04。根据浓度 -反应曲线对ATP、α,β-MeATP、β,γ-MeATP和2-MeSATP单次移动(100微摩尔/升苏拉明)估计的Kb值分别为52.3±20.2微摩尔/升、25.2±4.5微摩尔/升、21.7±11.0微摩尔/升和11.6±2.7微摩尔/升。7. 在静息张力下,P2Y嘌呤能受体选择性拮抗剂活性蓝2(100微摩尔/升)和P1嘌呤能受体选择性拮抗剂8-(对-磺基苯基)茶碱(8-SPT)(1微摩尔/升)不拮抗对α,β-MeATP(0.5 - 5微摩尔/升)的收缩反应。对ATP(50 - 500微摩尔/升)的收缩反应不受8-SPT(1微摩尔/升)影响,但被活性蓝2(100微摩尔/升)增强。8. 张力升高时,ATP和2-MeSATP引起舒张作用。ATP的这种作用不受河豚毒素(TTX)(0.5微摩尔/升)或苏拉明(100微摩尔/升)影响,但被活性蓝2(100微摩尔/升)和8-SPT(1微摩尔/升)拮抗,提示有抑制性P2y和P1嘌呤能受体参与。相反,α,β-MeATP和β,γ-MeATP仅引起收缩。α,β-MeATP的这种收缩作用对TTX(0.5微摩尔/升)有抗性,被苏拉明(100微摩尔/升)拮抗。9. 总之,猫结肠环形平滑肌含有介导收缩的节后α1肾上腺素能受体和P2X嘌呤能受体以及介导舒张的P2y和P1嘌呤能受体。节后α2肾上腺素能受体似乎不存在。

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