应用BRL 37344、cyanopindolol和sr59230a对兔离体空肠非典型β-肾上腺素受体的表征

A. MacDonald, K. Watt
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引用次数: 9

摘要

本研究采用β3-肾上腺素受体选择性激动剂BRL 37344、β3-肾上腺素受体阻断拮抗剂cyanopindolol和β3-肾上腺素受体新型选择性拮抗剂SR 59230A,进一步探讨兔空肠中β-肾上腺素受体的性质。2异丙肾上腺素对兔空肠自发收缩产生浓度依赖性抑制,pD2为7.14。普萘洛尔(1 μm)使异丙肾上腺素浓度-响应曲线(CRC)向右移动,浓度比为5.85,远远小于对经典β-肾上腺素受体的作用(估计pA2为6.66)。BRL 37344也产生浓度依赖性自发收缩抑制,pD2为7.41。心得安(1 μm)对BRL 37344 CRC无影响。在普萘洛尔(1 μm)的作用下,异丙肾上腺素CRC向右偏移(浓度比为21)。Cyanopindolol也使BRL 37344 CRC向右移位(浓度比为38)。这些变化与cyanopindolol对β3-肾上腺素受体的亲和力一致(估计对异丙肾上腺素和BRL 37344的pA2值分别为7.27和7.38)。在普萘洛尔(1 μm)存在的情况下,SR 59230A使异丙肾上腺素CRC呈浓度依赖性右移。Schild图给出的pA2值为7.16,尽管回归线的斜率与unity有显著差异(0.65)。SR 59230A也产生BRL 37344 CRC的浓度依赖性移位。Schild图的pA2为7.58,回归线斜率与unity无显著差异(0.81)。6 β3-肾上腺素受体的存在介导兔空肠自发收缩的松弛,这与心得安对异丙肾上腺素的拮抗作用相对较差、BRL 37344的松弛作用以及青观多洛尔和SR 59230A对异丙肾上腺素和BRL 37344的拮抗作用有关。SR 59230A对异丙肾上腺素缺乏竞争性拮抗作用,但对BRL 37344没有拮抗作用,这可能表明存在不止一个非典型β-肾上腺素受体群体。
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Characterisation of the atypical β-adrenoceptor in rabbit isolated jejunum using BRL 37344, cyanopindolol and SR 59230A

1 The present study was carried out to further investigate the nature of the β-adrenoceptor in rabbit jejunum using BRL 37344, a selective β3-adrenoceptor agonist, cyanopindolol, a β-adrenoceptor antagonist with blocking activity at β3-adrenoceptors and SR 59230A, a new selective β3-adrenoceptor antagonist.

2 Isoprenaline produced a concentration-dependent inhibition of the spontaneous contractions of rabbit jejunum with a pD2 of 7.14. Propranolol (1 μm) shifted the isoprenaline concentration-response curve (CRC) to the right with a concentration-ratio of 5.85, considerably less than would be expected for an action at classical β-adrenoceptors (estimated pA2 6.66).

3 BRL 37344 also produced a concentration-dependent inhibition of spontaneous contractions with a pD2 of 7.41. The BRL 37344 CRC was unaffected by propranolol (1 μm).

4 In the presence of propranolol (1 μm), cyanopindolol (1 μm) shifted the isoprenaline CRC to the right (concentration-ratio of 21). Cyanopindolol also shifted the BRL 37344 CRC to the right (concentration-ratio of 38). These shifts are consistent with the affinity of cyanopindolol for β3-adrenoceptors (estimated pA2 values of 7.27 and 7.38 against isoprenaline and BRL 37344, respectively).

5 In the presence of propranolol (1 μm), SR 59230A produced a concentration-dependent rightward shift of the isoprenaline CRC. The Schild plot gave a pA2 value of 7.16, although the slope of the regression line was significantly different from unity (0.65). SR 59230A also produced a concentration-dependent shift of the BRL 37344 CRC. The Schild plot gave a pA2 of 7.58 with the slope of the regression line not significantly different from unity (0.81).

6 The presence of β3-adrenoceptors mediating relaxation of spontaneous contractions in rabbit jejunum is supported by the relatively poor antagonism of isoprenaline by propranolol, the relaxant effect of BRL 37344 and the antagonism of isoprenaline and BRL 37344 by cyanopindolol and SR 59230A. The lack of simple competitive antagonism of isoprenaline, but not BRL 37344, by SR 59230A may suggest more than one population of atypical β-adrenoceptor.

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Issue Information Autonomic and Autacoid Pharmacology: Goodbye and thank you Attenuation of the anti-contractile effect of cooling in the rat aorta by perivascular adipose tissue Retraction: Dopamine receptor immunohistochemistry in the rat choroid plexus. Issue Information
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