Bird I M, Smith A D, Schulster D
Department of Endocrinology, National Institute for Biological Standards and Control, Potters Bar, Herts, U.K.
J Lipid Mediat. 1990 Nov-Dec;2(6):343-54.
Changes in the soluble inositol-containing metabolites of phosphoinositides have been measured in rat adrenal fasciculata reticularis cells stimulated by ACTH1-39 and ACTH5-24 (an analogue which is able to elicit maximal steroidogenesis in the absence of any discernible increase in cyclic AMP output). Small but significant increases in the total inositol-containing metabolites were found in response to stimulation with both ACTH analogues. For ACTH5-24 this effect on phosphoinositide (PI) metabolism occurred over the same dose range as that for the stimulation of steroidogenesis (with an ED50 of 10(-8) M ACTH5-24 for both effects). It is concluded that in the absence of cyclic AMP generation, ACTH5-24 increased the total inositol-containing metabolites in direct accordance with its steroidogenic capabilities. For ACTH1-39, the effect on PI metabolism reached a maximum with 10(-12) M ACTH1-39 and declined at higher concentrations, i.e., precisely those associated with increased cyclic AMP accumulation. These and the previous observations suggest that the cyclic AMP generated by ACTH1-39 may influence and inhibit the ACTH1-39 effect on PI metabolism. HPLC identification of the phosphoinositide metabolites of the adrenal cells showed that they include glycerophosphoinositol and glycerophosphoinositol phosphate (which would arise by sequential action of phospholipase A1 or A2 and lysophospholipase). Stimulation with ACTH1-39 elicited small but significant increases in glycerophosphoinositol levels, indicating that a phospholipase A may have been activated.
在促肾上腺皮质激素1 - 39（ACTH1 - 39）和促肾上腺皮质激素5 - 24（ACTH5 - 24，一种在不引起环磷酸腺苷（cAMP）输出有任何明显增加的情况下能够引发最大类固醇生成的类似物）刺激的大鼠肾上腺束状带网状细胞中，已对含肌醇的磷酸肌醇可溶性代谢产物的变化进行了测量。在用两种促肾上腺皮质激素类似物刺激后，发现含肌醇的代谢产物总量有小幅但显著的增加。对于ACTH5 - 24，这种对磷酸肌醇（PI）代谢的作用发生在与刺激类固醇生成相同的剂量范围内（两种作用的半数有效剂量（ED50）均为10⁻⁸ M ACTH5 - 24）。得出的结论是，在不产生环磷酸腺苷的情况下，ACTH5 - 24根据其类固醇生成能力直接增加了含肌醇的代谢产物总量。对于ACTH1 - 39，对PI代谢的作用在10⁻¹² M ACTH1 - 39时达到最大值，并在更高浓度下下降，即恰好是那些与环磷酸腺苷积累增加相关的浓度。这些以及先前的观察结果表明，ACTH1 - 39产生的环磷酸腺苷可能影响并抑制ACTH1 - 39对PI代谢的作用。肾上腺细胞磷酸肌醇代谢产物的高效液相色谱（HPLC）鉴定表明，它们包括甘油磷酸肌醇和甘油磷酸肌醇磷酸（这将通过磷脂酶A1或A2以及溶血磷脂酶的顺序作用产生）。用ACTH1 - 39刺激导致甘油磷酸肌醇水平有小幅但显著的增加，表明磷脂酶A可能已被激活。
