Chini E N, Beers K W, Chini C C, Dousa T P
Department of Physiology, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA.
Am J Physiol. 1995 Oct;269(4 Pt 1):C1042-7. doi: 10.1152/ajpcell.1995.269.4.C1042.
Cyclic ADP-ribose (cADPR) is a potent mediator of Ca2+ mobilization from intracellular stores in sea urchin eggs. However, the regulation of the cADPR-induced Ca2+ release system is not yet fully elucidated. We now report that spermine and related polyamines, in physiological concentrations, were able to inhibit the Ca2+ release induced by cADPR in sea urchin egg homogenate bioassays, as measured using the Ca2+ indicator fluo 3, but had no effect on the Ca2+ release induced by D-myo-inositol 1,4,5-trisphosphate (IP3) or by nicotinate adenine dinucleotide phosphate (NAADP). Spermine was a more potent inhibitor of the cADPR-induced Ca2+ release than spermidine and putrescine. Spermine inhibited not only the release induced by cADPR but also the Ca2+ release induced by caffeine and ryanodine. Finally, pretreatment of the sea urchin egg homogenates with caffeine or Sr2+ and Ca2+ prevented the inhibitory effect of spermine on cADPR-induced Ca2+ release. We propose that polyamines, which are present in millimolar concentrations in fertilized eggs, are specific inhibitors of the ryanodine channel and perhaps may serve as endogenous regulators of the cADPR-induced Ca2+ release system.
环磷酸腺苷核糖(cADPR)是海胆卵中从细胞内储存库动员钙离子的一种有效介质。然而,cADPR诱导的钙离子释放系统的调控尚未完全阐明。我们现在报告,在生理浓度下,精胺和相关多胺能够在海胆卵匀浆生物测定中抑制cADPR诱导的钙离子释放,这是使用钙离子指示剂fluo 3测量的,但对D-肌醇1,4,5-三磷酸(IP3)或烟酸腺嘌呤二核苷酸磷酸(NAADP)诱导的钙离子释放没有影响。精胺比亚精胺和腐胺更有效地抑制cADPR诱导的钙离子释放。精胺不仅抑制cADPR诱导的释放,还抑制咖啡因和雷诺丁诱导的钙离子释放。最后,用咖啡因或Sr2+和Ca2+预处理海胆卵匀浆可防止精胺对cADPR诱导的钙离子释放的抑制作用。我们提出,在受精卵中以毫摩尔浓度存在的多胺是雷诺丁通道的特异性抑制剂,也许可以作为cADPR诱导的钙离子释放系统的内源性调节剂。