Assender J W, Southgate K M, Hallett M B, Newby A C
Department of Cardiology, University of Wales College of Medicine, Heath Park, Cardiff, U.K.
Biochem J. 1992 Dec 1;288 ( Pt 2)(Pt 2):527-32. doi: 10.1042/bj2880527.
The effects on cellular proliferation and Ca2+ mobilization of analogues of cyclic AMP (cAMP) and cyclic GMP (cGMP) and of agents that elevate the intracellular concentrations of cyclic nucleotides were compared in closely similar preparations of first-passage rabbit aortic vascular smooth-muscle cells. Proliferation induced by foetal-bovine serum was inhibited by 78% by 1 mM-8-bromo cAMP and by 42% by 1 mM-8-bromo cGMP. In the presence of 100 microM-isobutylmethylxanthine, 100 microM-forskolin increased intracellular cAMP concentration 5-fold and inhibited proliferation by 87%, but did not affect cGMP concentration or cell viability (ATP concentration). Similarly in the presence of 100 microM-isobutylmethylxanthine, 1 mM-SIN-1 (3-morpholinosydnonimine) elevated cGMP concentration 4-fold and inhibited proliferation by 48%, but did not affect cAMP or ATP concentration. Isobutylmethylxanthine (1 mM) elevated cAMP concentration by 3-fold and cGMP concentration by 20-fold and inhibited proliferation by 81%. Concentrations of 8-bromo cAMP, 8-bromo cGMP, forskolin or SIN-1 that inhibited proliferation did not affect the elevation of intracellular free Ca2+ concentration caused by 2% (v/v) foetal-bovine serum, 100 nM-5-hydroxytryptamine or 10 nM-angiotensin II. The results demonstrate that elevation of intracellular cAMP and cGMP concentrations both independently inhibit vascular smooth-muscle cell proliferation, but these effects on proliferation are not mediated by inhibition of Ca2+ mobilization.
在首次传代的兔主动脉血管平滑肌细胞的极为相似的制剂中，比较了环磷酸腺苷（cAMP）和环磷酸鸟苷（cGMP）类似物以及提高细胞内环核苷酸浓度的试剂对细胞增殖和Ca2+动员的影响。1 mM - 8 - 溴环磷酸腺苷使胎牛血清诱导的增殖受到78%的抑制，1 mM - 8 - 溴环磷酸鸟苷使其受到42%的抑制。在存在100 μM异丁基甲基黄嘌呤的情况下，100 μM福司可林使细胞内cAMP浓度增加5倍，并使增殖受到87%的抑制，但不影响cGMP浓度或细胞活力（ATP浓度）。同样，在存在100 μM异丁基甲基黄嘌呤的情况下，1 mM - SIN - 1（3 - 吗啉代 sydnonimine）使cGMP浓度增加4倍，并使增殖受到48%的抑制，但不影响cAMP或ATP浓度。1 mM异丁基甲基黄嘌呤使cAMP浓度增加3倍，使cGMP浓度增加20倍，并使增殖受到81%的抑制。抑制增殖的8 - 溴环磷酸腺苷、8 - 溴环磷酸鸟苷、福司可林或SIN - 1的浓度，并不影响由2%（v/v）胎牛血清、100 nM 5 - 羟色胺或10 nM血管紧张素II引起的细胞内游离Ca2+浓度的升高。结果表明，细胞内cAMP和cGMP浓度的升高均能独立抑制血管平滑肌细胞增殖，但这些对增殖 的影响并非通过抑制Ca2+动员介导。
