STIMULATION OF GLYCOGENOLYSIS BY 3 LOCUST ADIPOKINETIC HORMONES INVOLVES G(S) AND CAMP

STIMULATION OF GLYCOGENOLYSIS BY 3 LOCUST ADIPOKINETIC HORMONES INVOLVES G(S) AND CAMP
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DOI:
10.1016/0303-7207(94)03438-y
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发表时间:
1995-02-01
影响因子:
4.1
通讯作者:
VANDERHORST, DJ
VANDERHORST, DJ
中科院分区:
医学2区
文献类型:
--
作者:
VROEMEN, SF;VANMARREWIJK, WJA;VANDERHORST, DJ

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昆虫脂肪运动激素(AKH)通过激活糖原磷酸化酶来动员脂肪体碳水化合物。本研究进一步阐明了飞蝗AKH-I、-II和-III的信号转导途径。我们表明,AKH增强脂肪体cAMP水平在体外。对于所有激素,1分钟后达到最大水平,与静息水平相比增加了200%。虽然大剂量AKH-I、-II和-III诱导的cAMP水平是相等的,但当以生理剂量施用时,AKH-III是最有效的。这种效力差异也适用于糖原磷酸化酶活化。霍乱毒素(CTX)同样增强cAMP水平和磷酸化酶活性,然而百日咳毒素(PTX)没有影响。CTX和AKH诱导的增加不是累加的,表明它们共享相同的途径。鸟苷-5 '-O-(2-硫代二磷酸)(GDP β S)强烈减弱AKH对磷酸化酶的激活。这些结果证明了cAMP在AKH信号转导中的作用,并表明AKH受体通过刺激性鸟嘌呤核苷酸结合蛋白(G(s))与cAMP形成和糖原磷酸化酶活化偶联。
Insect adipokinetic hormones (AKHs) have been shown to mobilize fat body carbohydrate by glycogen phosphorylase activation. In this study, the signal transduction pathways of AKH-I, -II and -III from the migratory locust are further elucidated. We show that the AKHs enhance fat body cAMP levels in vitro. For all hormones, maximal levels are reached after 1 min and correspond to a 200% increase compared to resting levels. Although cAMP levels induced by massive doses of AKH-I, -II and -III are equal, AKH-III is the most potent when applied in a physiological dose. This difference in potency also applies to glycogen phosphorylase activation. Cholera toxin (CTX) likewise enhances cAMP levels and phosphorylase activity, however pertussis toxin (PTX) has no effect. Increases induced by CTX and AKH are not additive, suggesting that they share the same pathway. Phosphorylase activation by the AKHs is strongly attenuated by guanosine-5'-O-(2-thiodiphosphate) (GDP beta S). These results demonstrate a role for cAMP in AKH signal transduction and indicate that the AKH receptor(s) are coupled to cAMP formation and glycogen phosphorylase activation via the stimulatory guanine nucleotide-binding protein (G(s)).