Ruck A, Millns P, Kendall D A, Hill S J
Department of Physiology and Pharmacology, Medical School, Queen's Medical Centre, Nottingham, U.K.
Biochem Pharmacol. 1990 Nov 15;40(10):2371-5. doi: 10.1016/0006-2952(90)90735-4.
The effect of isoprenaline on cyclic AMP accumulation has been investigated in the rat neuronal cell line B50 and the rat astrocytoma cell line C6. Noradrenaline and isoprenaline stimulated cyclic AMP accumulation in both cell lines. Isoprenaline (0.5 microM; EC50 = 0.1 microM) produced a rapid (T1/2 = 1.3 min) increase in [3H]cyclic AMP accumulation in B50 cells while the response to isoprenaline (0.1 microM; EC50 = 0.01 microM) in C6 cells was somewhat slower (T1/2 = 7.5 min). The response to 0.5 microM isoprenaline was antagonized by both propranolol (IC50 = 8.4 +/- 1.6 nM; N = 3) and the beta 2-selective antagonist ICI 118551 (IC50 = 2.1 +/- 0.2 nM; N = 6). However, no attenuation of the response to isoprenaline (0.5 microM) was observed at concentrations of the beta 1-adrenoceptor antagonist atenolol up to 10 microM (N = 3). In contrast, in C6 cells, which have previously been shown to possess beta 1-adrenoceptors, atenolol inhibited isoprenaline-induced (0.1 microM) cyclic AMP accumulation (IC50 = 2.0 +/- 0.5 microM; N = 6). Furthermore, the beta 2-selective antagonist ICI 118551 was much less potent in the C6 cell line (IC50 = 0.2 +/- 0.05 microM; N = 3) than in the B50 cells. In conclusion, the present data suggest that isoprenaline mediates cyclic AMP accumulation in the neuronal cell line via activation of beta 2-adrenoceptors, while in the astrocytoma cell line the cyclic AMP response is mediated by beta 1-adrenoceptors.
已在大鼠神经元细胞系B50和大鼠星形细胞瘤细胞系C6中研究了异丙肾上腺素对环磷酸腺苷(cAMP)积累的影响。去甲肾上腺素和异丙肾上腺素均刺激了这两种细胞系中的cAMP积累。异丙肾上腺素(0.5微摩尔/升;半数有效浓度[EC50]=0.1微摩尔/升)使B50细胞中[3H]cAMP的积累迅速增加(半衰期[T1/2]=1.3分钟),而C6细胞对异丙肾上腺素(0.1微摩尔/升;EC50=0.01微摩尔/升)的反应则稍慢(T1/2=7.5分钟)。普萘洛尔(半数抑制浓度[IC50]=8.4±1.6纳摩尔/升;N=3)和β2选择性拮抗剂ICI 118551(IC50=2.1±0.2纳摩尔/升;N=6)均拮抗了对0.5微摩尔/升异丙肾上腺素的反应。然而,在高达10微摩尔/升的β1肾上腺素能受体拮抗剂阿替洛尔浓度下,未观察到对异丙肾上腺素(0.5微摩尔/升)反应的减弱(N=3)。相比之下,在先前已证明具有β1肾上腺素能受体的C6细胞中,阿替洛尔抑制了异丙肾上腺素诱导的(0.1微摩尔/升)cAMP积累(IC50=2.0±0.5微摩尔/升;N=6)。此外,β2选择性拮抗剂ICI 118551在C6细胞系中的效力(IC50=0.2±0.05微摩尔/升;N=3)远低于在B50细胞中的效力。总之,目前的数据表明,异丙肾上腺素通过激活β2肾上腺素能受体介导神经元细胞系中的cAMP积累,而在星形细胞瘤细胞系中,cAMP反应由β1肾上腺素能受体介导。