Agonist-induced cyclic ADP ribose production in airway smooth muscle

Cyclic ADP-ribose (cADPR) triggers sarcoplasmic reticulum (SR) Ca2+ release in airway smooth muscle (ASM). SR Ca2+ release is an important component of the intracellular Ca2+ ([Ca2+]i) response of ASM to agonists. Whether cADPR is endogenously produced in ASM during agonist stimulation has not been established. In this study, cADPR production was examined in acutely dissociated porcine ASM cells. ACh stimulation (⩾1 μM) significantly increased cADPR levels, peaking between 30 s and 1 min. This effect was inhibited by M2 and M3 muscarinic receptor antagonists. Histamine (⩾5 μM) increased cADPR levels to a greater extent than ACh, while diphenhydramine blocked histamine-induced cADPR elevation. Both bradykinin (100 nM) and endothelin-1 (100 nM) also increased cADPR levels to a greater extent than ACh or histamine. These results indicate that in porcine ASM, certain agonists acting via receptors increase cADPR levels. Furthermore, the extent of cADPR responses to agonist varies, possibly reflecting differences in G-protein coupling.