Siegl A M, Daly J W
J Cyclic Nucleotide Protein Phosphor Res. 1985;10(3):229-45.
Prostaglandin D2, 2-chloroadenosine, forskolin and combinations of these agents increase cyclic AMP-levels in intact human platelets. The inhibition of activated cyclic AMP-generating systems by 1) alpha2-adrenergic receptor-mediated hormonal input (norepinephrine), 2) a P-site agent (2',5'-dideoxyadenosine) and 3) a divalent cation (calcium) were examined: 1) Norepinephrine produces non-competitive inhibition of both forskolin and prostaglandin D2(PGD2)-stimulated cyclic AMP-accumulation in intact human platelets. The Ki values for norepinephrine versus forskolin, PGD2 and 2-chloroadenosine are similar in magnitude, while the Ki versus a forskolin-PGD2 combination is approximately 10-fold greater. Onset of inhibition by norepinephrine of the PGD2-response is several fold faster than for the forskolin-response. When platelets stimulated by the forskolin and PGD2 combination are exposed to norepinephrine, there is a transient increase in levels of cyclic AMP due to the potentiation of a minor beta-adrenergic component. This stimulation is followed by inhibition. 2) 2',5'-Dideoxyadenosine produces a non-competitive inhibition of the forskolin-response with a Ki of 110 microM. The inhibition of the PGD2-response by 2',5'-dideoxyadenosine is competitive with a Ki of 6-13 microM, while inhibition of the forskolin-PGD2 response has a Ki of 30 microM. Onset of inhibition by 2',5'-dideoxyadenosine is identical for forskolin or PGD2-stimulated platelets. There is a lag period for inhibition of platelets stimulated with the forskolin-PGD2 combination. The PGD2-forskolin combination appears to stabilize the cyclic AMP-generating system of platelets against inhibition by either norepinephrine or 2',5'-dideoxyadenosine. 3) Calcium ions cause a similar inhibition of cyclic AMP-generation in intact platelets, regardless of the type of stimulation.
前列腺素D2、2-氯腺苷、福斯高林以及这些药物的组合可提高完整人血小板中的环磷酸腺苷（cAMP）水平。研究了1）α2-肾上腺素能受体介导的激素输入（去甲肾上腺素）、2）P位点药物（2'，5'-二脱氧腺苷）和3）二价阳离子（钙）对激活的环磷酸腺苷生成系统的抑制作用：1）去甲肾上腺素对完整人血小板中福斯高林和前列腺素D2（PGD2）刺激的环磷酸腺苷积累产生非竞争性抑制。去甲肾上腺素对福斯高林、PGD2和2-氯腺苷的抑制常数（Ki）值在大小上相似，而对福斯高林-PGD2组合的Ki值大约大10倍。去甲肾上腺素对PGD2反应的抑制起效比对福斯高林反应快几倍。当受福斯高林和PGD2组合刺激的血小板暴露于去甲肾上腺素时，由于次要的β-肾上腺素能成分的增强作用，环磷酸腺苷水平会短暂升高。这种刺激之后是抑制。2）2'，5'-二脱氧腺苷对福斯高林反应产生非竞争性抑制，Ki为110微摩尔。2'，5'-二脱氧腺苷对PGD2反应的抑制是竞争性的，Ki为6-13微摩尔，而对福斯高林-PGD2反应的抑制Ki为30微摩尔。2'，5'-二脱氧腺苷对福斯高林或PGD2刺激的血小板的抑制起效相同。对福斯高林-PGD2组合刺激的血小板的抑制存在延迟期。PGD2-福斯高林组合似乎可稳定血小板的环磷酸腺苷生成系统，使其免受去甲肾上腺素或2'，5'-二脱氧腺苷的抑制。3）无论刺激类型如何，钙离子对完整血小板中环磷酸腺苷的生成产生类似的抑制作用。
