Hartzell H C, Machaca K, Hirayama Y
Department of Anatomy and Cell Biology, Emory University School of Medicine, Atlanta, Georgia 30322-3030, USA.
Mol Pharmacol. 1997 Apr;51(4):683-92. doi: 10.1124/mol.51.4.683.
Adenophostin-A, a novel compound isolated from cultures of Penicillium brevicompactum, has been shown to stimulate Ca2+ release from inositol-1,4,5-trisphosphate (IP3)-sensitive Ca2+ stores in microsomal preparations, permeabilized cells, and lipid vesicles containing purified IP3 receptor. The purpose of the current study was to compare the effects of adenophostin-A and IP3 on Ca2+ release from stores and Ca2+ influx in intact Xenopus laevis oocytes. Ca2+ influx though store-operated Ca2+ channels and Ca2+ release from stores were monitored by measuring two Ca2+ -activated Cl- currents that can be used as real-time indicators of Ca2+ release and Ca2+ influx (I(Cl-1) and I(Cl-2), respectively). We find that high concentrations (final intraoocyte concentrations of 5-10 microM) of adenophostin-A and IP3 stimulate a large Ca2+ release from stores (as measured by I(Cl-1)) followed by Ca2+ influx (as measured by I(Cl-2)). Low concentrations (approximately 50 nM) of IP3 stimulate oscillations in Ca2+ release without stimulating Ca2+ influx. In contrast, low concentrations of adenophostin-A can stimulate Ca2+ influx without stimulating a large Ca2+ release. However, Ca2+ influx did not occur in the complete absence of Ca2+ release. Therefore, it is unlikely that adenophostin-A directly stimulates store-operated Ca2+ channels. We hypothesize that adenophostin-A releases Ca2+ from a subpopulation of stores that is tightly coupled to store-operated Ca2+ channels.
腺嘌呤宿主素 - A是一种从短密青霉培养物中分离出的新型化合物，已被证明能刺激微粒体制剂、透化细胞以及含有纯化肌醇 - 1,4,5 - 三磷酸（IP3）受体的脂质小泡中，从对IP3敏感的Ca2 +储存库释放Ca2 +。本研究的目的是比较腺嘌呤宿主素 - A和IP3对非洲爪蟾完整卵母细胞中Ca2 +从储存库释放及Ca2 +内流的影响。通过测量两种Ca2 +激活的Cl -电流来监测经储存库操纵的Ca2 +通道的Ca2 +内流以及Ca2 +从储存库的释放，这两种电流可分别用作Ca2 +释放和Ca2 +内流的实时指标（分别为I(Cl-1)和I(Cl-2)）。我们发现，高浓度（卵母细胞内最终浓度为5 - 10 microM）的腺嘌呤宿主素 - A和IP3会刺激大量Ca2 +从储存库释放（通过I(Cl-1)测量），随后是Ca2 +内流（通过I(Cl-2)测量）。低浓度（约50 nM）的IP3刺激Ca2 +释放振荡但不刺激Ca2 +内流。相比之下，低浓度的腺嘌呤宿主素 - A可刺激Ca2 +内流而不刺激大量Ca2 +释放。然而，在完全没有Ca2 +释放的情况下不会发生Ca2 +内流。因此，腺嘌呤宿主素 - A不太可能直接刺激经储存库操纵的Ca2 +通道。我们推测，腺嘌呤宿主素 - A从与经储存库操纵的Ca2 +通道紧密偶联的一部分储存库中释放Ca2 +。
