Cyclic ADP-ribose stimulates sarcoplasmic reticulum calcium release in porcine coronary artery smooth muscle

Cyclic ADP-ribose (cADPR) was shown to induce calcium release from the endoplasmic reticulum via ryanodine-sensitive pathways. In smooth muscle, two pathways for calcium release from the sarcoplasmic reticulum (SR) have been previously demonstrated: D-myo-inositol 1,4,5-trisphosphate-gated and ryanodine-gated. However, evidence for cADPR as a regulator for SR Ca²⁺ release in smooth muscle is lacking. We used permeabilized porcine coronary artery smooth muscle cells to directly examine the stimulation of SR Ca²⁺ release by cADPR. The results provide direct evidence that cADPR stimulates SR Ca²⁺ release and that this response is not inhibited by heparin, by depletion of the caffeine-sensitive Ca²⁺ pool, or by blockade of ryanodine receptors. These results indicate a novel mechanism for Ca²⁺ release from the SR of vascular smooth muscle.