부산대학교 도서관

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.pharmthera.2005.03.003 Byline: A. Mark Evans, Christopher N. Wyatt, Nicholas P. Kinnear, Jill H. Clark, Elisa A. Blanco Keywords: NAADP; cADPR; ADP-ribosyl cyclase; Ryanodine receptor; Sarcoplasmic reticulum; Lysosomes; Artery; Smooth muscle Abbreviations: 8-bromo-cADPR, 8-bromo-cyclic adenosine diphosphate-ribose; ACh, acetylcholine; [beta]-NAD.sup.+, [beta]-nicotinamide adenine dinucleotide (oxidized form); [beta]-NADH, [beta]-nicotinamide adenine dinucleotide (reduced form); [beta]-NADP.sup.+, [beta]-nicotinamide adenine dinucleotide phosphate; BK.sub.Ca channel, Ca.sup.2+-activated potassium channel; cADPR, cyclic adenosine diphosphate-ribose; cAMP, cyclic adenosine monophosphate; cGDPR, cyclic guanosine diphosphate-ribose; cGMP, cyclic guanosine monophosphate; CICR, Ca.sup.2+-induced Ca.sup.2+ release; ER, endoplasmic reticulum; ET-1, endothelin-1; FKBP, FK-506 binding proteins; HPV, hypoxic pulmonary vasoconstriction; IP.sub.3, inositol 1,4,5 trisphosphate; IP.sub.3R, inositol 1,4,5 trisphosphate receptor; mAChR, muscarinic acetylcholine receptors; NAADP, nicotinic acid adenine dinucleotide phosphate; PGF.sub.2[alpha], prostaglandin F.sub.2[alpha]; PKA, protein kinase A; ROS, reactive oxygen species; RyR, ryanodine receptors; SERCA, sarcoplasmic/endoplasmic reticulum Ca.sup.2+ ATPase; SR, sarcoplasmic reticulum; STOC, spontaneous transient outward potassium current Abstract: It is generally accepted that the mobilisation of intracellular Ca.sup.2+ stores plays a pivotal role in the regulation of arterial smooth muscle function, paradoxically during both contraction and relaxation. However, the spatiotemporal pattern of different Ca.sup.2+ signals that elicit such responses may also contribute to the regulation of, for example, differential gene expression. These findings, among others, demonstrate the importance of discrete spatiotemporal Ca.sup.2+ signalling patterns and the mechanisms that underpin them. Of fundamental importance in this respect is the realisation that different Ca.sup.2+ storing organelles may be selected by the discrete or coordinated actions of multiple Ca.sup.2+ mobilising messengers. When considering such messengers, it is generally accepted that sarcoplasmic reticulum (SR) stores may be mobilised by the ubiquitous messenger inositol 1,4,5 trisphosphate. However, relatively little attention has been paid to the role of Ca.sup.2+ mobilising pyridine nucleotides in arterial smooth muscle, namely, cyclic adenosine diphosphate-ribose (cADPR) and nicotinic acid adenine dinucleotide phosphate (NAADP). This review will therefore focus on these novel mechanisms of calcium signalling and their likely therapeutic potential. Author Affiliation: Division of Biomedical Sciences, School of Biology, Bute Building, University of St. Andrews, St. Andrews, Fife KY16 9TS, UK