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首页> 外文期刊>Cellular Signalling >Functional properties of Ca2+-inhibitable type 5 and type 6 adenylyl cyclases and role of Ca2+ increase in the inhibition of intracellular cAMP content.
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Functional properties of Ca2+-inhibitable type 5 and type 6 adenylyl cyclases and role of Ca2+ increase in the inhibition of intracellular cAMP content.

机译:抑制Ca2 +的5型和6型腺苷酸环化酶的功能特性以及Ca2 +的作用增加了对细胞内cAMP含量的抑制作用。

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摘要

Among the different adenylyl cyclase (AC) isoforms, type 5 and type 6 constitute a subfamily which has the remarkable property of being inhibited by submicromolar Ca2+ concentrations in addition to Galphai-mediated processes. These independent and cumulative negative regulations are associated to a low basal enzymatic activity which can be strongly activated by Galphas-mediated interactions or forskolin. These properties ensure possible wide changes of cAMP synthesis. Regulation of cAMP synthesis by Ca2+ was studied in cultured or native cells which express naturally type 5 and/or type 6 AC, including well-defined renal epithelial cells. The results underline two characteristics of the inhibition due to agonist-elicited increase of intracellular Ca2+: i) Ca2+ rises achieved through capacitive Ca2+ entry or intracellular Ca2+ release can inhibit AC to a similar extent; and ii) in a same cell type, different agonists inducing similar overall Ca2+ rises elicit a variable inhibition of AC activity. The results suggest that a high efficiency of AC regulation by Ca2+ is linked to a requisite close localization of AC enzyme and Ca2+ rises.
机译:在不同的腺苷酸环化酶(AC)亚型中,类型5和类型6构成了一个亚家族,除了Galphai介导的过程外,还具有被亚微摩尔Ca2 +浓度抑制的显着特性。这些独立的和累积的负调控与低基础酶活性有关,其可以被Galphas介导的相互作用或毛喉素强烈激活。这些性质确保了cAMP合成的可能广泛变化。在培养的或天然表达天然5型和/或6型AC的细胞(包括明确定义的肾上皮细胞)中研究了Ca2 +对cAMP合成的调控。结果强调了激动剂引起的细胞内Ca2 +升高的抑制作用的两个特征:i)通过容性Ca2 +进入或细胞内Ca2 +释放而引起的Ca2 +升高可以在相似程度上抑制AC。 ii)在相同的细胞类型中,诱导相似的总体Ca2 +升高的不同激动剂引起对AC活性的可变抑制。结果表明,Ca2 +对AC的高效调节与必需的AC酶紧密定位有关,并且Ca2 +升高。

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