Akil M, Fisher S K
Neuroscience Laboratory, University of Michigan, Ann Arbor 48104-1687.
J Neurochem. 1989 Nov;53(5):1479-86. doi: 10.1111/j.1471-4159.1989.tb08541.x.
The possibility that an increased intracellular concentration of cyclic AMP (cAMP) can regulate the extent of muscarinic receptor-stimulated phosphoinositide (PPI) turnover in the human neuroblastoma cell line SK-N-SH was examined. Addition of either forskolin (or its water-soluble analog, L-85,8051), theophylline, isobutylmethylxanthine, or cholera toxin, agents that interact with either the catalytic unit of adenylate cyclase, cAMP phosphodiesterase, or the guanine nucleotide binding protein linked to adenylate cyclase activation, resulted in a 45-181% increase in cAMP concentration and a 27-70% inhibition of carbachol-stimulated inositol phosphate release. Through the use of digitonin-permeabilized cells, the site of inhibition was localized to a step at, or distal to, the guanine nucleotide binding protein that regulates phospholipase C activity. In contrast, when intact SK-N-SH cells were exposed to prostaglandin E1, the ensuing increases in cAMP were not accompanied by an inhibition of stimulated PPI turnover. These differential effects of increased cAMP concentrations on stimulated PPI turnover may reflect the compartmentation of cAMP within SK-N-SH cells.
研究了细胞内环磷酸腺苷（cAMP）浓度升高是否能调节人神经母细胞瘤细胞系SK-N-SH中毒蕈碱受体刺激的磷酸肌醇（PPI）周转程度。添加福斯可林（或其水溶性类似物L-85,8051）、茶碱、异丁基甲基黄嘌呤或霍乱毒素，这些与腺苷酸环化酶催化单位、cAMP磷酸二酯酶或与腺苷酸环化酶激活相关的鸟嘌呤核苷酸结合蛋白相互作用的试剂，导致cAMP浓度增加45%-181%，并使卡巴胆碱刺激的肌醇磷酸释放受到27%-70%的抑制。通过使用洋地黄皂苷通透细胞，抑制位点定位于调节磷脂酶C活性的鸟嘌呤核苷酸结合蛋白处或其远端的一个步骤。相反，当完整的SK-N-SH细胞暴露于前列腺素E1时，随后cAMP的增加并未伴随着刺激的PPI周转受到抑制。cAMP浓度升高对刺激的PPI周转的这些不同影响可能反映了SK-N-SH细胞内cAMP的区室化。
