Stimulus-transcription coupling in catecholamine synthesis

长期刺激或持续应激可引起交感神经元和肾上腺髓质中儿茶酚胺生物合成的限速酶酪氨酸羟化酶活性增加。本研究以体外培养的牛肾上腺髓质细胞为模型，研究了细胞刺激-信号转导系统、细胞刺激-儿茶酚胺合成偶联和酪氨酸羟化酶mRNA的转录调控。关于（A），我们报道了（1）冈田酸长时间处理通过抑制培养的肾上腺髓质细胞中的Ca^<2+>内流减少卡巴胆碱诱导的儿茶酚胺分泌，（2）藜芦碱引起肾上腺髓质细胞中二酰基甘油形成和蛋白激酶C向膜转位的Ca^<2 +>依赖性增加，（3）在肾上腺髓质细胞中，冈田酸长时间处理可使肾上腺髓质细胞中的二酰基甘油形成和蛋白激酶C向膜转位增加，（4）冈田酸长时间处理可使肾上腺髓质细胞中的二酰基甘油形成和蛋白激酶C向膜转位增加。 关于我们 终髓细胞和（3）星形孢菌素有效地抑制Ca^2+/钙调素依赖性蛋白激酶II。关于（B），我们报道了（4）脑钠肽刺激细胞周期蛋白GMP的产生和酪氨酸羟化酶的活性，（5）海胆毒素抑制烟碱乙酰胆碱受体介导的儿茶酚胺合成和分泌，（6）锂处理通过激活蛋白激酶C刺激培养的肾上腺髓质细胞的儿茶酚胺合成和分泌。关于（C），我们观察到（7）冈田酸刺激培养的肾上腺髓质细胞酪氨酸羟化酶的活性，但减弱其mRNA的水平;（8）高渗NaCl培养基增强酪氨酸羟化酶的活性和mRNA。值得注意的是，酪氨酸羟化酶的活性和mRNA水平之间存在关系，但并不总是如此。肾上腺髓质、交感神经元和脑中酪氨酸羟化酶的细胞刺激-转录偶联有待进一步研究。少

Long-term stimulation or persistent stress produces an in-crease in activity of tyrosine hydroxylase, the rate-limiting enzyme of catecholamine biosynthesis, in the sympathetic neurons and the adrenal medulla. The precise mechanism, however, still remains to be determined how cell stimulation increases the enzyme activity or protein (enzyme induction).In the present study, we used cultured bovine adrenal medullary cells as a model for catecholaminergic neuron and investigated as follows ; (A) cell stimulation-signal stransduction system, (B) cell stimulation-catecholamine synthesis coupling and (C) transcriptional regulation of tyrosine hydroxylase mRNA. Concerning about (A), we reported that (1) long treatment with okadaic acid reduced carbachol-evoked secretion of catecholamines by inhibiting Ca^<2+> influx in cultured adrenal medullary cells, (2) veratridine caused the Ca^<2+> -dependent increase in diacylglycerol formation and translocation of protein kinase C to memtbranes in adre … More nal medullary cells and (3) staurosporine effectively inhibited Ca^<2+> /calmodulin-dependent protein kinase II. Concerning about (B), we reported that (4) Brain natriuretic peptide stimulated the production of cyclin GMP and the activity of tyrosine hydroxylase in the cells, (5) sea urchin toxin inhibited nicotinic acetylcholine receptor-mediated synthesis and secretion of catecholamines and (6) lithium treatment stimulated catecholamine synthesis and secretion via activation of protein kinase C in cultured adrenal medullary cells. Concerning about (C), we observed that (7) okadaic acid stimulated the activity of tyrosine hydroxylase but attenuated the level of its mRNA and (8) hypertonic NaCl medium enhanced both the activity and mRNA of tyrosine hydroxylase in cultured adrenal medullary cells. It is interesting to note that there is a relationship between the activity and the mRNA level of tyrosine hydroxylase but not always. We must further study the coupling for cell stimulation-transcription of tyrosine hydroxylase in adrenal medulla as well as sympathetic neurons and the brain. Less