Woodcock E A, Little P J, Tanner J K
Baker Medical Research Institute, Prahan, Victoria, Australia.
Biochem J. 1990 Nov 1;271(3):791-6. doi: 10.1042/bj2710791.
Endothelin has steroidogenic activity in adrenal glomerulosa cells, as do two other vasoconstrictor peptides, angiotensin II and vasopressin. The steroidogenic activities of angiotensin II and vasopressin are probably mediated via the phosphatidylinositol-turnover pathway and associated changes in cytosolic Ca2+ concentration. Endothelin caused a steroidogenic response, which was small compared with that to angiotensin II and quantitatively similar to the vasopressin response. Cytosolic free Ca2+ responses were similarly higher to angiotensin II than to either of the other two peptides. However, total inositol phosphate responses to endothelin and angiotensin II were similar when these were measured over 20 min, and were quantitatively greater than the vasopressin response. A detailed study has been made of the phosphatidylinositol-turnover response to endothelin in comparison with responses to angiotensin II and vasopressin. Each of the three peptides produced a rapid and transient rise in Ins(1,4,5)P3 (max. 5-15 s), followed by a slow sustained rise. Ins(1,4,5)P3 was metabolized by both dephosphorylation and phosphorylation pathways, but the relative importance of the two metabolic pathways was different under stimulation by each of the three peptides. These findings show that adrenal glomerulosa cells can distinguish between the stimulation of phosphatidylinositol turnover by three different effectors. These differences in the pathway may be associated with the observed different steroidogenic and Ca2+ responses to the three peptides.
内皮素在肾上腺球状带细胞中具有类固醇生成活性,另外两种血管收缩肽——血管紧张素II和加压素也是如此。血管紧张素II和加压素的类固醇生成活性可能是通过磷脂酰肌醇代谢途径以及胞质Ca2+浓度的相关变化介导的。内皮素引起了类固醇生成反应,与血管紧张素II相比该反应较小,在数量上与加压素反应相似。胞质游离Ca2+对血管紧张素II的反应同样高于对其他两种肽的反应。然而,当在20分钟内测量时,内皮素和血管紧张素II的总肌醇磷酸反应相似,并且在数量上大于加压素反应。与血管紧张素II和加压素的反应相比,已经对内皮素的磷脂酰肌醇代谢反应进行了详细研究。三种肽中的每一种都使Ins(1,4,5)P3迅速短暂升高(最大5 - 15秒),随后缓慢持续升高。Ins(1,4,5)P3通过去磷酸化和磷酸化途径进行代谢,但在三种肽各自刺激下,这两种代谢途径的相对重要性不同。这些发现表明,肾上腺球状带细胞能够区分三种不同效应物对磷脂酰肌醇代谢的刺激。该途径中的这些差异可能与观察到的三种肽不同的类固醇生成和Ca2+反应有关。