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Muscarinic acetylcholine receptors in NG108-15 neuroblastoma x glioma cells, and ?-adrenergic or angiotensin II receptors in cortical astrocytes and/or ventricular myocytes, utilize the direct signaling pathway to ADP-ribosyl cyclase within cell membranes to produce cyclic ADP-ribose (cADPR) from ?-NAD + . This signal cascade is analogous to the previously established transduction pathways from bradykinin receptors to phospholipase C? and ?-adrenoceptors to adenylyl cyclase via G proteins. Upon receptor stimulation, the newlyformed cADPR may coordinately function to upregulate the release of Ca 2+  from the type II ryanodine receptors as well as to facilitate Ca 2+  influx through voltage-dependent Ca 2+  channels. cADPR interacts with FK506, an immunosuppressant, at FKBP12.6, FK506-bindingprotein, and calcineurin, or ryanodine receptors. cADPR also functions through activating calcineurin released from Akinase anchoring protein (AKAP79). Thus, some G q/11 coupled receptors can control cADPR-dependent modulation in Ca 2+  signaling.

Signal Transduction from Bradykinin, Angiotensin, Adrenergic and Muscarinic Receptors to Effector Enzymes, Including ADP-Ribosyl Cyclase