磷酸二酯酶同工酶Ⅲ和Ⅳ调节气管平滑肌环腺苷酸的区域化分布

磷酸二酯酶同工酶Ⅳ（ＰＤＥⅣ）抑制剂咯利普兰（Ｒｏｌ，３０μｍｏｌ·Ｌ－１）对３０μｍｏｌ·Ｌ－１异丙肾上腺素所致的犬气管平滑肌环腺苷酸（ｃＡＭＰ）积聚的增强作用比ＰＤＥⅢ抑制剂氰胍哒嗪（ＳＫＦ９４８３６，３０μｍｏｌ·Ｌ－１）要强，但对异丙肾上腺素所致的犬气管平滑肌松弛的增强作用比ＳＫＦ９４８３６要弱．３０μｍｏｌ·Ｌ－１Ｒｏｌ或ＳＫＦ９４８３６对３０μｍｏｌ·Ｌ－１福斯科林所致的犬气管平滑肌松弛与ｃＡＭＰ积聚的增强作用程度几乎相等．异丙肾上腺素，福斯科林单独或与ＳＫＦ９４８３６，Ｒｏｌ合用都仅引起犬气管平滑肌的可溶部ｃＡＭＰ积聚，对颗粒部ｃＡＭＰ含量无明显影响．上述结果提示犬气管平滑肌存在着ｃＡＭＰ的区域化分布，它受ＰＤＥⅢ，ＰＤＥⅣ的调节，而与平滑肌细胞的亚细胞结构无关     

磷酸二酯酶同工酶Ⅲ和Ⅳ调节气管平滑肌环腺鞋酸的区…

磷酸二酯酶同工酶Ⅳ（ＰＤＥⅣ）抑制剂咯利普兰（Ｒｏｌ，３０μｍｏｌ·Ｌ＾－１）对３０μｍｏｌ·Ｌ＾－１异丙肾上腺素所致的犬气管平滑肌环腺苷酸（ｃＡＭＰ）积聚的增强作用比ＰＤＥⅢ抑制剂氰腺哒嗪（ＳＫＦ９４８３６，３０μｍｏｌ·Ｌ－１）要强，但对异丙肾上腺素所致的犬气管平滑肌松弛的增强作用比ＳＫＦ９４８３６要弱。３０μｍｏｌ·Ｌ＾－１Ｒｏｌ或ＳＫＦ９４８３６对３０μｍｏｌ·Ｌ＾－１福斯科林所致的犬气管     

扎普司特和谷胱甘肽翻转豚鼠离体气管对硝普钠的耐受性

上皮完整或去上皮的豚鼠离体气管以３００μｍｏｌ·Ｌ－１硝普钠（ＳＮＰ）预处理１ｈ，使ＳＮＰ对抗乙醋甲胆碱气管收缩作用的剂量反应曲线右移１．３－１．５倍，最大舒张率下降４１％－５８％，形成ＳＮＰ气管松弛作用的耐受性．８－溴环鸟苷酸可模拟ＳＮＰ在豚鼠离体气管形成的ＳＮＰ耐受性，谷胱甘肽（１ｍｍｏｌ·Ｌ－１）及环核苷酸磷酸二酯酶（ＰＤＥ）Ⅴ抑制剂扎普司特（３０μｍｏｌ·Ｌ－１）均可部分翻转ＳＮＰ的气管松弛作用耐受性，而蛋白合成抑制剂环己酰亚胺（１０μｍｏｌ·Ｌ－１）对ＳＮＰ的耐受性无预防作用．结果表明ＳＮＰ可产生豚鼠离体气管松弛耐受性，这可能是由于气管平滑肌中环鸟苷酸（ｃＧＭＰ）积聚而下调鸟苷酸环化酶（ＧＣ）活性和上调ＰＤＥⅤ活性．     

咯利普兰逆转豚鼠离体气管对沙丁胺醇的耐受性

本研究目的旨在观察ＰＤＥＩＶ抑制剂咯利普兰对沙丁胺醇（ＳＢ）耐受性的影响。用豚鼠离体气管标本，预先接触ＳＢ１μｍｏｌ·Ｌ－１，１ｈ可使ＳＢ对抗乙酰甲胆碱气管收缩作用的剂量反应曲线右移５倍，最大松弛率下降３０％，形成ＳＢ气管松弛作用的耐受性。磷酸二酯酶（ＰＤＥ）ＩＶ抑制剂咯利普兰能翻转ＳＢ气管松弛作用的耐受性，但ＰＤＥＩＩ抑制剂氰胍哒嗪则不能。虽然蛋白合成抑制剂环己酰亚胺对ＳＢ耐受性无预防作用，但上述结果仍提示ＳＢ气管松弛作用的耐受性可能与ＰＤＥＩＶ活性的增高有关。     

洛土辛对心肌动作电位及犬浦肯野纤维慢内电流的影响

目的　探讨洛土辛（Ｌｏｔ）对心肌动作电位（ＡＰ）及犬浦肯野纤维（ＰＦ）慢内向电流（Ｉｓｉ）的影响和其在正性肌力效应中所起的作用。方法　采用标准微电极及双微电极电压钳技术。结果　Ｌｏｔ１～１００μｍｏｌ·Ｌ－１可剂量依赖性地延长豚鼠乳头肌状快反应ＡＰ的ＡＰＤ２０和ＡＰＤ９０,增加收缩力（Ｆｃ）;在利血平化豚鼠乳头状肌,Ｌｏｔ对ＡＰＤ２０和Ｆｃ的影响较未经Ｒｅｓ化组减弱。在豚鼠左房肌,Ｌｏｔ３０μｍｏｌ·Ｌ－１可明显地削弱Ａｃｈ缩短ＡＰＤ５０和降低Ｆｃ的作用。Ｌｏｔ３～１００μｍｏｌ·Ｌ－１可剂量依赖性地增加高Ｋ＋去极化诱发的豚鼠乳头状肌及兔窦房结慢反应ＡＰ的ＡＰＡ、Ｖｍａｘ;对兔ＡＰＤ５０和窦房结周长（Ｓｉｎｕｓｃｙｃｌｅｌｅｎｇｔｈ,ＳＣＬ）却无明显影响。在犬ＰＦ,Ｌｏｔ３０μｍｏｌ·Ｌ－１时间依赖性及剂量依赖性地（３～１００μｍｏｌ·Ｌ－１）增加Ｉｓｉ。结论　Ｌｏｔ有延长ＡＰＤ和促钙内流作用,且在其正性肌力效应的产生中起着重要作用,而这些作用的产生与其抑制ＰＤＥⅢ有关。     

淫羊藿总黄酮对肾上腺素能受体阻断作用的研究

淫羊藿总黄酮（ＴＦＥ，０，１３ｇ·Ｌ－１）抑制兔离体右心房肌的肌力和心率，此作用无Ｍ受体激动效应和钙拮抗作用，能使异丙肾上腺素（ＩＳＯ，１０－７ｍｏｌ·Ｌ－１）对心房肌的正性频率作用的量效曲线平行右移。ＴＦＥ不影响ＩＳＯ（１０－７ｍｏｌ·Ｌ－１）对豚鼠气管条的负性肌力作用和去甲肾上腺素（ＮＥ，１０－６ｍｏｌ·Ｌ－１）对兔主动脉条的正性肌力作用。ＴＦＥ（ｉｖ，１００ｍｇ·ｋｇ－１）明显降低麻醉猫和大鼠血压，减弱ＩＳＯ（１０μｇ·ｋｇ－１）所致的大鼠心率加快的作用，但对ＩＳＯ和肾上腺素（Ａｄｒ）的降压作用无影响，也不增敏Ａｄｒ的升压作用。实验结果证实ＴＦＥ选择性阻断离体及整体动物心肌β１受体，对气管β２受体和血管平滑肌α受体无阻断作用。     

大鼠脂肪细胞β受体亚型的研究

用异丙肾上腺素（ＩＳＯＰ）和非典型β受体激动剂ＢＲＬ３７３４４作用于大鼠脂肪细胞，测定所产生的ｃＡＭＰ含量，结果二种激动剂的量效曲线相似。ＩＳＯＰ和ＢＲＬ３７３４４的ＥＣ５０分别为２．３×１０－７ｍｏｌ·Ｌ－１和２．０×１０－７ｍｏｌ·Ｌ－１，二者的ＥＣ８０都是１０－６ｍｏｌ·Ｌ－１。在普萘洛尔（ＰＲＯＰ）和选择性β１受体阻断剂ＣＧＰ２０７１２Ａ存在的情况下，ＩＳＯＰ的作用被阻断，ＰＲＯＰ与ＣＧＰ２０７１２Ａ的ＩＣ５０分别为２．０×１０－７ｍｏｌ·Ｌ－１和５．０×１０－８ｍｏｌ·Ｌ－１。但ＰＲＯＰ及ＣＧＰ２０７１２Ａ却难以阻断ＢＲＬ３７３４４的作用，只有在很高浓度（１０－４ｍｏｌ·Ｌ－１）时才能阻断其作用。上述结果表明大鼠脂肪细胞上存在着β１受体和非典型的β受体。     

萘甲异喹对大鼠主动脉平滑肌~（45）Ca转运的影响

萘甲异喹（ＮＩ１，１０μｍｏｌ·Ｌ－１）和硝苯吡啶（Ｎｉｆ０．５μｍｏｌ·Ｌ－１）对大鼠主动脉平滑肌４５Ｃａ溢流无影响，ＮＩ（１～３０μｍｏｌ·Ｌ－１）能浓度依赖地抑制高钾和苯肾上腺素引起的大鼠主动脉平滑肌４５Ｃａ内流，抑制率分别为２７％～８１％和１７％～７７％，ＮＩ（１０μｍｏｌ·Ｌ－１）尚可明显抑制由苯肾上腺素引起的４５Ｃａ外溢。这些结果提示ＮＩ能抑制平滑肌细胞膜ＰＤＣ和ＲＯＣ两类钙通道及细胞内钙释放。     

EDRF对NE引起的大鼠主动脉缩血管效应的作用

目的：研究ＥＤＲＦ（ｅｎｄｏｔｈｅｌｉｕｍ－ｄｅｒｉｖｅｄｒｅｌａｘｉｎｇｆａｃｔｏｒ，ＥＤＲＦ）对ＮＥ（ｎｏｒｅｐｉｎｅｐｈｒｉｎｅ，ＮＥ）引起的大鼠主动脉收缩反应的影响。方法：内皮完整和去内皮的大鼠主动脉环悬挂在器官浴槽中，测定血管的张力和收缩速度的变化。所有的实验在吲哚美辛（ｉｎｄｏｍｅｔｈａｃｉｎ，１０μｍｏｌ·Ｌ－１）和普萘洛尔（ｐｒｏｐｒａｎｏｌｏｌ，３μｍｏｌ·Ｌ－１）存在下进行。结果：用甲烯蓝（ｍｅｔｈｙｌｅｎｅｂｌｕｅ，ＭＢ，１０μｍｏｌ·Ｌ－１）和左旋硝基精氨酸（ＮＧ－ｎｉｔｒｏ－Ｌ－ａｒｇｉｎｉｎｅ，Ｌ－ＮＮＡ，３０μｍｏｌ·Ｌ－１）处理内皮完整的大鼠主动脉环，ＮＥ的剂量－收缩曲线明显左移。ＥＣ３０值均降低７倍，最大反应比值分别为１．６±０．３和１．７±０．４。在去内皮的大鼠主动脉环中，经ＭＢ与Ｌ－ＮＮＡ处理后，仍可见ＥＣ３０下降３倍，最大反应比值分别为１．１±０．６和１．１±０．４。后者可能与血管平滑肌产生少量ＥＤＲＦ有关。结论：结果提示，ＮＥ对血管的收缩反应也受血管内皮和平滑肌产生的ＥＤＲＦ的调控。     

大鼠肝和心脏微粒体羧酸酯酶的诱导与抑制

用对硝基苯醋酸酯（ｐ－ＮＰＡ）为底物，测定大鼠肝和心脏敌酸醋酶（ＣＥ）的水解活性，苯巴比妥和氟贝特对肝脏ＣＥ活力有明显的诱导作用，而地塞米松（Ｄｅｘ）对心脏ＣＥ活力显示有诱导作用，表明相同药物对肝和心脏ＣＥ活力诱导是有差异的：双－对硝基苯磷酸酯钠（ＢＮＰＰ），苯甲基磺酰氟（ＰＭＳＦ）和氟磷酸二异丙酯（ＤＦＰ）对肝和心脏ＥＣ活力均有明显的抑制作用，ＢＮＰＰ，ＰＭＳＦ和ＤＦＰ对肝及心脏ＣＥ活力的Ｉ５０分别为１００，２００，５μｍｏｌ·Ｌ－１和５０．０，５．０、０１ｍｍｏｌ·Ｌ－１；对肝和心脏ＣＥ水解ｐ－ＮＰＡ的Ｋｉ分别为１．１．１．２．０．６７ｍｍｏｌ·Ｌ－１和１．０，０．８．０．５４ｍｍｏｌ·Ｌ－１，结果表明三种抑制剂对肝和心脏ＣＥ的抑制强度存在明显差异．     

扎普司特和谷胱甘肽翻转豚鼠离体气管对硝普钠的耐受性

上皮完整或去上皮的豚鼠离体气管以300 μmol·L^-1硝普钠(SNP)预处理1 h,使SNP对抗乙醋甲胆碱气管收缩作用的剂量反应曲线右移1.3-1.5 倍, 最大舒张率下降41%-58%,形成SNP气管松弛作用的耐受性. 8-溴环鸟苷酸可模拟SNP在豚鼠离体气管形成的SNP耐受性, 谷胱甘肽(1 mmol·L^-1)及环核苷酸磷酸二酯酶(PDE) Ⅴ抑制剂扎普司特(30 μmol·L^-1)均可部分翻转SNP 的气管松弛作用耐受性,而蛋白合成抑制剂环己酰亚胺(10 μmol·L^-1)对SNP的耐受性无预防作用.结果表明SNP可产生豚鼠离体气管松弛耐受性, 这可能是由于气管平滑肌中环鸟苷酸(cGMP)积聚而下调鸟苷酸环化酶(GC)活性和上调PDEⅤ活性.     

Inhibition of pig aortic smooth muscle cell DNA synthesis by selective type III and type IV cyclic AMP phosphodiesterase inhibitors.

Foetal calf serum (FCS) and platelet-derived growth factor (PDGF)-stimulated incorporation of [3H]thymidine into pig aortic smooth muscle cell (ASMC) DNA was decreased by agents that either stimulated the synthesis (forskolin) or inhibited the breakdown (3-isobutyl-1-methylxanthine, IBMX) of cAMP. FCS-stimulated incorporation of [3H]thymidine into DNA was also reduced by selective inhibitors of cAMP-specific phosphodiesterase (PDE IV) (Ro-20-1724, rolipram) and cGMP-inhibited cAMP PDE (PDE III) (SK&F 94836). IBMX, Ro-20-1724, rolipram and SK&F 94836 enhanced forskolin inhibition of DNA synthesis. Alone, rolipram was a relatively weak inhibitor of FCS-induced ASMC DNA synthesis (IC25 greater than 20 microM); however, in the presence of a threshold concentration of SK&F 94836 (20 microM), the potency of rolipram increased (IC25 = 4 microM), suggesting synergy in the actions of PDE III and PDE IV inhibitors. SK&F 94836 and rolipram elicited 30% and 37%, respectively, reductions in FCS-induced ASMC proliferation and potentiated the inhibitory actions of forskolin. PDE III and PDE IV inhibitors alone, exerted minimal effects on ASMC cAMP levels after a short term (10 min) or long-term (2 or 24 hr) exposure, but enhanced forskolin-induced accumulation of cAMP. ASMC spontaneously released cAMP into the extracellular medium, a process that was increased by forskolin. PDE III and PDE IV inhibitors had no effect alone on cAMP extrusion but enhanced the effect of forskolin. Exposure of ASMC to forskolin or SK&F 94836 for 15 min increased the activity ratio (AR) of cAMP-dependent protein kinase from 0.05 to 0.17 and 0.23, respectively. Ro-20-1724, alone, did not affect cAMP-dependent protein kinase but enhanced the stimulatory effect of forskolin (AR = 0.37) and SK&F 94836 (AR = 0.27). Agents that increased cGMP synthesis (glycerol trinitrate, atrial natriuretic factor) or decreased its hydrolysis by selectively inhibiting cGMP-specific PDE (PDE V) (zaprinast) exerted no effects on FCS- or PDGF-stimulated [3H]thymidine incorporation into DNA either alone or in combination. The cytosolic fraction of pig ASMC contained four cyclic nucleotide PDEs which were categorized as PDE V, Ca2+/calmodulin-stimulated PDE (PDE I), PDE III and PDE IV. PDE I and III activities were also associated with the particulate fraction. The results demonstrate that inhibitors of PDEs III and IV alone or in combination with forskolin, reduce ASMC DNA synthesis and proliferation, through an action likely to involve elevation of intracellular cAMP. In contrast, inhibition of cGMP hydrolysing PDE subtypes (I and V) exerted no effect on DNA synthesis in this cell type.     

谷氨酸触发大鼠大脑皮质神经元Ca~(2+)内流与PTK的关系

目的　研究谷氨酸 (glutamate,Glu)触发大鼠大脑皮质神经元Ca2 + 内流特性 ,蛋白酪氨酸激酶 (PTK)抑制剂genistein及蛋白酪氨酸磷酸酶 (PTP)抑制剂vanadate对其影响 ,揭示PTK与Glu触发大鼠大脑皮质神经元Ca2 + 内流的内在联系。方法　采用Fura 2 /AM荧光测定胞浆Ca2 + 变化技术 ,在原代培养的大鼠大脑皮质神经元上观察药物对Glu触发Ca2 + 内流的影响。结果　Glu触发的Ca2 + 内流不受电压依赖性钙通道 (VDCC)阻断剂尼莫地平影响 ,亦不受非VDCC阻断剂SK&F96 36 5影响 ,但可被PTK抑制剂genis tein抑制 ,被PTP抑制剂vanadate增强。genistein(1～ 30μmol·L-1)呈浓度依赖性抑制Glu触发的Ca2 + 内流。vana date则浓度依赖性增强Glu触发的Ca2 + 内流。结论　对尼莫地平敏感的VDCC及对SK&F96 36 5敏感的非VDCC没有参与Glu触发的Ca2 + 内流。PTK激活参与了Glu触发的Ca2 + 内流     

Role of cyclic nucleotide phosphodiesterase isozymes in intact canine trachealis.

The role of individual cyclic nucleotide phosphodiesterase (PDE) isozymes in regulating cAMP and cGMP content in intact canine trachealis was examined using isozyme-selective and nonselective PDE inhibitors. The inhibitors used in this study were characterized previously [Mol. Pharmacol. 37:206-214 (1990)] and included: 1) zaprinast, an inhibitor (Ki = 0.1 microM) of the cGMP-specific PDE (cAMP Km = 135 microM; cGMP Km = 4 microM); 2) SK&F 94120, an inhibitor (Ki = 7 microM) of the cGMP-inhibited PDE (cAMP Km = 0.3 microM; cGMP Km = 8 microM); 3) Ro 20-1724, an inhibitor (Ki = 5 microM) of the cAMP-specific PDE (cAMP Km = 4 microM; cGMP Km = 40 microM); and 4) 3-isobutyl-1-methylxanthine (IBMX), a nonselective PDE inhibitor (IC50 = 1-30 microM). In addition to the aforementioned isozymes, canine trachealis contains a Ca2+/calmodulin-stimulated PDE (cAMP Km = 1 microM; cGMP Km = 2 microM) and a GMP-stimulated PDE (cAMP Km = 93 microM; cGMP Km = 60 microM), for which selective inhibitors are not available. Isolated canine trachealis strips were contracted with methacholine and exposed to various concentrations of PDE inhibitors, before being relaxed by the cumulative addition of isoproterenol, an adenylate cyclase activator, or sodium nitroprusside, a guanylate cyclase activator. At the completion of the concentration-response studies, tissues were flash-frozen and assayed for cyclic nucleotide content. Neither isoproterenol-induced relaxation nor cAMP accumulation was altered by zaprinast, but both of these responses were potentiated by pretreatment of tissues with either SK&F 94120 or Ro 20-1724. The effects of SK&F 94120 and Ro 20-1724 were additive, and the combination of SK&F 94120, Ro-1724, and IBMX had no greater effect on the responses to isoproperenol than did either IBMX alone or the combination of SK&F 94120 plus Ro 20-1724. In contrast, zaprinast potentiated sodium nitroprusside-induced relaxation and cGMP accumulation, whereas neither SK&F 94120 nor Ro 20-1724 altered these responses. IBMX produced a greater potentiation than did zaprinast, and the combination of zaprinast and IBMX had a greater effect than either agent alone. The results of this study suggest that the cGMP-inhibited and cAMP-specific PDEs are responsible for cAMP hydrolysis in intact canine trachealis, whereas cGMP hydrolysis is mediated by the cGMP-specific PDE as well as the Ca2+/calmodulin-stimulated PDE and/or the cGMP-stimulated PDE.     

酪氨酸激酶抑制剂对cyclopiazoni cacid引起的大鼠主动脉血管环收缩效应的影响

目的　探讨酪氨酸激酶在Ca2 +池操纵性Ca2 +内流中的作用。方法　记录大鼠胸主动脉环收缩反应。结果　①不同剂量酪氨酸激酶抑制剂 genistein (1～ 10 0 μmol·L-1)和tyrphostin 2 5 (Tyr 2 5 ,1～ 30 μmol·L-1)均以浓度依赖性抑制cyclopiazonicacid (CPA)引起的平滑肌收缩平台期。Tyr 2 5的最大作用浓度为 10 μmol·L-1,抑制率为 42 %±11%。② 10 μmol·L-1Tyr 2 5和 1μmol·L-1nifedipine(Nif)对CPA引起电压依赖性Ca2 +通道 (VDCC)开放过程的抑制作用存在部分交叉。③ 1μmol·L-1Nif预处理阻断VDCC作用后 ,10 μmol·L-1Tyr 2 5只能部分阻断CPA引起的Ca2 +池操纵性Ca2 +通道 (SOCC)开放过程 ,再加入 6 0 μmol·L-1SK&F96 36 5可完全阻断SOCC的开放过程。结论　CPA引起平滑肌的收缩过程中 ,蛋白质酪氨酸激酶参与了开启VDCC和SOCC的信号转导过程     

Anti-spasmogenic activity of isoenzyme-selective phosphodiesterase inhibitors in guinea-pig trachealis.

1 The anti-spasmogenic potential of SK&F 94120 (PDE3-selective), rolipram (PDE4-selective), zaprinast (PDE5-selective), zardaverine (dual PDE3/4 inhibitor) and theophylline (non-selective) was evaluated in guinea-pig trachealis. 2 SK&F 94120 or rolipram (10 and 100 microM) antagonized histamine-induced tension generation in a concentration-dependent and non-competitive manner whereas ACh-induced contractions were unaffected. Similarly, SK&F 94120 and rolipram in combination were anti-spasmogenic with respect to both contractile agonists to an extent that was greater than the effect of either drug alone. Identical results were obtained with zardaverine (1, 10 and 100 microM) and theophylline (100 microM and 1 mM). 3 Zaprinast protected guinea-pig trachealis against histamine-, but not ACh-induced contractile responses in a manner that was indistinguishable from the results obtained with SK&F 94120. However, in contrast to the interaction between SK&F 94120 and rolipram, no further antagonism was seen when zaprinast and rolipram were used in combination. 4 Pre-treatment of tissues with SNP (10 and 100 microM) antagonized histamine-induced tension generation in a concentration-dependent and non-competitive manner. However, no further antagonism was produced when SNP and rolipram were used concurrently. Likewise, the protection afforded by a combination SNP and SK&F 94120 was no greater than that produced by SNP alone. 5 These results demonstrate that an inhibitor of PDE3 enhances the anti-spasmogenic activity of rolipram but not drugs that elevate cyclic GMP mass. Moreover, the ability of SNP and zaprinast to protect guinea-pig trachealis against histamine-induced contractions apparently is not due to the inhibition of PDE3.     

Relaxation of guinea-pig trachea by cyclic AMP phosphodiesterase inhibitors and their enhancement by sodium nitroprusside.

1. The effects of agents that elevate either cyclic AMP (the phosphodiesterase (PDE) III inhibitor siguazodan, salbutamol) or cyclic GMP (sodium nitroprusside (SNP)) on the relaxant activity of the PDE IV inhibitor, rolipram, were investigated in carbachol (0.1 microM) precontracted guinea-pig tracheal sheets. 2. Rolipram, siguazodan and SNP caused concentration-related reductions in tone of tissues precontracted with 0.1 microM carbachol (EC50 values 12.5; 2.73 and 0.35 microM respectively). Whilst the concentration-response relationship for the PDE III inhibitor, siguazodan, was monophasic that of the PDE IV inhibitor, rolipram, was biphasic. 3. The relaxant activity of rolipram was markedly enhanced in the presence of 10 microM siguazodan (EC50 < 0.01 microM), 0.1 microM salbutamol (EC50 0.03 microM) and 0.3 microM SNP (EC50 0.03 microM). In contrast, the relaxant activity of siguazodan was unaffected by SNP and only modestly enhanced by rolipram (10 microM) and salbutamol (0.1 microM). 4. The relaxant activity of SNP was enhanced by the PDE V inhibitor SK&F 96231 (30 microM: EC50 0.06 microM) and rolipram (30 microM, EC50 0.08 microM) but was unaffected by 30 microM siguazodan. 5. At concentrations up to 10 microM, neither siguazodan nor rolipram elevated tracheal cyclic AMP levels. However, the combination of 10 microM rolipram and siguazodan caused a two fold increase in the cyclic AMP content (from 2.19 to 4.36 pmol cyclic AMP mg-1 protein). SNP (0.1-10 microM) failed to produce a significant increase in tracheal cyclic AMP levels. At 0.1 microM the effect of SNP on tracheal cyclic AMP levels was significantly (P < 0.05) increased in the presence of rolipram but not siguadozan.(ABSTRACT TRUNCATED AT 250 WORDS)     

异紫堇定的扩血管作用与环核苷酸的关系(英文)

应用血管平滑肌等张收缩和放射免疫测定环核苷酸水平等方法研究了异紫堇定扩血管作用及其机理 .结果表明 ,异紫堇定浓度依赖性地松弛去甲肾上腺素 (NE ,1μmol·L- 1)和KCl(30mmol·L- 1)预收缩的兔胸主动脉螺旋条 ,EC50 分别为 (12 .6± 4 .4 )和 (447± 38) μmol·L- 1,对NE的作用比对KCl强 36倍 .亚甲蓝 (10 μmol·L- 1)可部分抑制异紫堇定的扩血管作用 ,但不受格列本脲 ,吲哚美辛 ,普萘洛尔或N L 硝基精氨酸影响 .异紫堇定还可促进cGMP生成增加 ,并可被亚甲蓝完全阻断 .异紫堇定对cAMP的生成无影响 .结果提示 ,异紫堇定的扩血管作用至少部分通过激活鸟苷酸环化酶 ,促进cGMP的生成实现