Mittag T W, Guo W B, Taniguchi T
Department of Ophthalmology, Mount Sinai School of Medicine, CUNY, New York 10029.
Biochem Pharmacol. 1993 Mar 24;45(6):1311-6. doi: 10.1016/0006-2952(93)90284-4.
Vanadate (VO3-) was found to activate adenylyl cyclase (AC) in ocular ciliary process membrane. This response was additive to that of isoproterenol (ISO) and vasoactive intestinal peptide (VIP), but it was potentiative with forskolin (FSK) and also with Ca2+/calmodulin activation of AC activity. The potentiated response of FSK in the presence of VO3- was due to an increase in Vmax without a change in the apparent affinity of FSK or VO3-, and therefore differs from the potentiated response of activated G-protein (Gs) and FSK, where the affinity of FSK was increased by 1-2 orders of magnitude. Potentiation occurred at low Mg2+ and was not observed at free [Mg2+] > 3 mM. Iodate (IO3-) inhibited the FSK, ISO, and VO3- activations of AC in ciliary process membranes (IC50, 0.3 mM). In vivo topical treatment of the rabbit eye with 50 microL of 5% NaIO3 had no effect alone but completely blocked the intraocular pressure response to a 50-microL topical dose of 1% FSK and partially blocked the response to a 50-microL dose of 0.001% ISO. These findings indicate that some AC enzymes may have a binding site for oxyanions which can directly regulate enzyme activity.
钒酸盐（VO3-）可激活眼睫状体膜中的腺苷酸环化酶（AC）。这种反应与异丙肾上腺素（ISO）和血管活性肠肽（VIP）的反应具有加和性，但与福斯可林（FSK）以及Ca2+/钙调蛋白激活AC活性时具有协同作用。在VO3-存在的情况下，FSK的协同反应是由于Vmax增加，而FSK或VO3-的表观亲和力没有变化，因此与激活的G蛋白（Gs）和FSK的协同反应不同，在后者中FSK的亲和力增加了1-2个数量级。协同作用在低镁离子浓度下发生，在游离[Mg2+]>3 mM时未观察到。碘酸盐（IO3-）抑制睫状体膜中AC的FSK、ISO和VO3-激活作用（IC50，0.3 mM）。用50微升5%的NaIO3对兔眼进行体内局部治疗单独无作用，但完全阻断了对50微升1% FSK局部剂量的眼压反应，并部分阻断了对50微升0.001% ISO剂量的反应。这些发现表明，一些AC酶可能具有一个氧阴离子结合位点，该位点可直接调节酶活性。
