Galione A, White A, Willmott N, Turner M, Potter B V, Watson S P
University Department of Pharmacology, University of Oxford, UK.
Nature. 1993 Sep 30;365(6445):456-9. doi: 10.1038/365456a0.
Many hormones or neurotransmitters act at cell surface receptors to increase the intracellular free calcium concentration, triggering a wide range of cellular responses. As the source of this Ca2+ is often internal stores, additional messengers are required to convey the hormonal message from the plasma membrane. Cyclic ADP-ribose (cADPR) has been proposed as the endogenous activator of Ca(2+)-induced Ca2+ release by the ryanodine receptor in sea urchin eggs and in several mammalian cell types. A second messenger role for cADPR requires that its intracellular levels be under the control of extracellular stimuli. Here we demonstrate a novel action of 3',5'-cyclic guanosine monophosphate (cGMP) in stimulating the synthesis of cADPR from beta-NAD+ by activating its synthetic enzyme ADP-ribosyl cyclase in sea urchin eggs and egg homogenates. We suggest that cADPR may transduce signals generated by cell surface receptors or gaseous transmitters linked to cGMP production.
许多激素或神经递质作用于细胞表面受体，以增加细胞内游离钙浓度，从而引发广泛的细胞反应。由于这种Ca2+的来源通常是细胞内储存库，因此需要额外的信使将激素信息从质膜传递过来。环ADP核糖（cADPR）被认为是海胆卵和几种哺乳动物细胞类型中通过ryanodine受体诱导Ca2+释放的内源性激活剂。cADPR的第二信使作用要求其细胞内水平受细胞外刺激的控制。在这里，我们证明了3',5'-环鸟苷单磷酸（cGMP）在海胆卵和卵匀浆中通过激活其合成酶ADP核糖基环化酶来刺激从β-NAD+合成cADPR的新作用。我们认为cADPR可能转导由细胞表面受体或与cGMP产生相关的气体递质产生的信号。
