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首页> 外文期刊>Cellular Signalling >Activation of particulate guanylate cyclase by adrenomedullin in cultured SV-40 transformed cat iris sphincter smooth muscle (SV-CISM-2) cells
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Activation of particulate guanylate cyclase by adrenomedullin in cultured SV-40 transformed cat iris sphincter smooth muscle (SV-CISM-2) cells

机译：肾上腺髓质素在培养的SV-40转化猫虹膜括约肌平滑肌（SV-CISM-2）细胞中激活鸟苷酸环化酶

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We investigated the effects of adrenomedullin (ADM) on cGMP production in cultured SV-40 transformed cat iris sphincter smooth muscle (SV-CISM2) cells. ADM increased cGMP accumulation in a time- (t(1/2) = 3.5 min) and concentration- (EC50 = 200 nM) dependent manner. The peptide increased cGMP formation in the transformed cells by 405-fold as compared to 1.6-fold in primary cultured CISM cells. The basal cGMP concentrations in both cell types were comparable. In addition, ADM increased cAMP accumulation in SV-CISM-2 cells and in primary cultured cells by 18.9- and 5.8-fold, respectively. The ADM receptor antagonist, ADM(26-52), but not the atrial natriuretic peptide (ANP) receptor antagonist, anantin, inhibited ADM-induced cGMP formation. The phorbol ester, phorbol 12, 13-dibutyrate (E'DBu), which inhibits particulate guanylate cyclases in smooth muscle, blocked ADM-stimulated cGMP accumulation. In contrast, inhibitors of the soluble guanylate cyclases, such as LY83583 and ODQ, and inhibitors of the nitric oxide cascade had little effect on ADM-stimulated cGMP production. The stimulatory effect of ADM on cGMP formation is due to activation of the guanylate cyclase system and not to a much reduced phosphodiesterase activity. ADM stimulated guanylate cyclase activity in membrane fractions isolated from SV-CISM-2 cells in a concentration-dependent manner with EC50 value of 72 nM. Pertussis toxin, an activator of the G-protein, Gi, inhibited ADM-stimulated cGMP accumulation, whereas cholera toxin, a stimulator of the Gs G-protein and subsequently cAMP accumulation, had little effect. Pretreatment of the plasma membrane fraction with Gi alpha antibody attenuated ADM-stimulated guanylate cyclase activity by 75%. We conclude that ADM increases intracellular cGMP levels in SV-CISM-2 cells through activation of the ADM receptor and subsequent stimulation of a Gi-mediated membrane-bound guanylate cyclase. (C) 2000 Elsevier Science Inc. All rights reserved. [References: 25]
机译：我们调查了肾上腺髓质素（ADM）对培养的SV-40转化猫虹膜括约肌平滑肌（SV-CISM2）细胞cGMP产生的影响。 ADM以时间（t（1/2）= 3.5分钟）和浓度（EC50 = 200 nM）依赖性的方式增加了cGMP的积累。与原代培养的CISM细胞中的1.6倍相比，该肽使转化细胞中的cGMP形成增加了405倍。两种细胞类型中的基础cGMP浓度相当。此外，ADM使SV-CISM-2细胞和原代培养细胞中的cAMP积累分别增加了18.9倍和5.8倍。 ADM受体拮抗剂ADM（26-52）而非心房利钠肽（ANP）受体拮抗剂anantin抑制ADM诱导的cGMP形成。佛波酯，佛波12、13-二丁酸佛波酯（E'DBu）抑制平滑肌中的鸟苷酸环化酶，阻止ADM刺激的cGMP积累。相反，可溶性鸟苷酸环化酶的抑制剂，例如LY83583和ODQ，以及一氧化氮的抑制剂，对ADM刺激的cGMP生成几乎没有影响。 ADM对cGMP形成的刺激作用是由于鸟苷酸环化酶系统的激活而不是磷酸二酯酶活性的大大降低。 ADM以浓度依赖性方式刺激了从SV-CISM-2细胞分离的膜级分中的鸟苷酸环化酶活性，其EC50值为72 nM。百日咳毒素，一种G蛋白的活化剂，Gi，抑制了ADM刺激的cGMP积累，而霍乱毒素，一种Gs G蛋白的刺激，随后是cAMP的积累，几乎没有作用。用Gi alpha抗体对质膜部分进行预处理可使ADM刺激的鸟苷酸环化酶活性降低75％。我们得出结论，ADM通过激活ADM受体并随后刺激Gi介导的膜结合鸟苷酸环化酶来增加SV-CISM-2细胞中的细胞内cGMP水平。 （C）2000 Elsevier Science Inc.保留所有权利。 [参考：25]

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