Lee H C
Department of Pharmacology, University of Minnesota, Minneapolis, Minnesota 55455, USA.
Annu Rev Pharmacol Toxicol. 2001;41:317-45. doi: 10.1146/annurev.pharmtox.41.1.317.
Cyclic ADP-ribose (cADPR) and nicotinic acid adenine dinucleotide phosphate (NAADP) are two Ca(2+) messengers derived from NAD and NADP, respectively. Although NAADP is a linear molecule, structurally distinct from the cyclic cADPR, it is synthesized by similar enzymes, ADP-ribosyl cyclase and its homolog, CD38. The crystal structure of the cyclase has been solved and its active site identified. These two novel nucleotides have now been shown to be involved in a wide range of cellular functions including: cell cycle regulation in Euglena, a protist; gene expression in plants; and in animal systems, from fertilization to neurotransmitter release and long-term depression in brain. A battery of pharmacological reagents have been developed, providing valuable tools for elucidating the physiological functions of these two novel Ca(2+) messengers. This article reviews these recent results and explores the implications of the existence of multiple Ca(2+) messengers and Ca(2+) stores in cells.
环磷酸腺苷核糖（cADPR）和烟酰胺腺嘌呤二核苷酸磷酸（NAADP）是分别由NAD和NADP衍生而来的两种钙离子信使。尽管NAADP是一种线性分子，在结构上与环状的cADPR不同，但它是由类似的酶，即ADP核糖环化酶及其同源物CD38合成的。环化酶的晶体结构已被解析，其活性位点也已确定。现已表明，这两种新型核苷酸参与了广泛的细胞功能，包括：原生生物眼虫的细胞周期调控；植物中的基因表达；以及在动物系统中，从受精到神经递质释放和大脑中的长期抑制。已经开发出一系列药理学试剂，为阐明这两种新型钙离子信使的生理功能提供了有价值的工具。本文综述了这些最新结果，并探讨了细胞中多种钙离子信使和钙离子储存存在的意义。
