Cyclic ADP - ribose increases Ca 2 + removal in smooth muscle Karen

Ca 2+ release from the sarcoplasmic reticulum (SR) via the ryanodine receptor (RyR) regulates both general cellular activities such as metabolism and more specific events such as smooth muscle contraction. RyR opening is itself promoted by Ca 2+ (Endo et al., 1970; Fabiato, 1983) and decreased by FK506 binding proteins (FKBPs) (Brillantes et al., 1994; Xin et al., 2002). Among other substances, proposed to modulate RyR activity and release Ca 2+ from the SR, cADPR has received considerable attention. Evidence supports such a regulatory role for cADPR in several cell types including sea urchin eggs, macrophages, neurones, myocytes and pancreatic The wide distribution of enzymes for its synthesis (ADP-ribosyl cyclase) and degradation (cADPR hydrolase) has been cited in support of this activity (Lee, 2001). Further evidence is the observation that cADPR might also act as a second messenger in the response to acetylcholine (ACh), For example, in smooth muscle, cADPR increased and a cADPR inhibitor (8-amino-cADPR) blocked the amplitude and frequency of ACh-induced Ca 2+ oscillations (Prakash et al., 1998). cADPR also released Ca 2+ from the SR in both renal and coronary artery cells (Kannan et al., 1996; Li et al., 2000) and longitudinal intestinal smooth muscle (Kuemmerle and Makhlouf, 1995) and increased RyR activity in lipid bilayers (Li et al., 2001) though extreme conditions e.g. low ATP concentrations and high [Ca 2+ ] might be necessary (Sitsapesan