The functional roles of Ca 2+ mobilizing pyridine nucleotides cADPR and NAADP in detrusor and taenia caceum

Agonists such as muscarinic receptor activators are normally thought to induce contraction in smooth muscle through IP 3 production and release of Ca 2+ from sarcoplasmic reticulum (SR). However, cADPR and NAADP may also be involved in this process, the former acting on the SR, the latter on lysosome‐related organelles. This study investigated the functions of cADPR and NAADP, and their roles in carbachol (CCh) contractions in β‐escin permeabilized guinea pig detrusor and taenia caecum. IP 3 (50 μM), cADPR (50 μM) and NAADP (1 μM) induced contraction in both tissues. Heparin (1 mg/ml) blocked contractions by IP 3 but not by cADPR or NAADP. Thapsigargin (T, 5 μM) + ryanodine (R, 100 μM) inhibited responses to both cADPR and IP 3 , but not to NAADP. NAADP contractions were blocked by inhibitors bafilomycin (0.1 μM) or high concentration of NAADP (100 μM). CCh (50 μM) contraction in both tissues was reduced by heparin but not completely abolished. T + R were able to abolish this CCh response in taenia, but T + R + NAADP (100 μM) were necessary to completely abolish the contraction in detrusor. These results show that cADPR and NAADP have a role in Ca 2+ signalling in detrusor and taenia. While IP 3 and cADPR are important in CCh contractions in both tissues, NAADP is involved only in detrusor. Thus, key differences in Ca 2+ signalling mechanisms are apparent between two different smooth muscles of the same species. Supported by Wellcome Trust.