Signal transduction from bradykinin, angiotensin, adrenergic and muscarinic receptors to effector enzymes, including ADP-ribosyl cyclase

Muscarinic acetylcholine receptors in NG108-15 neuroblastoma x glioma cells, and β-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 β-NAD⁺. This signal cascade is analogous to the previously established transduction pathways from bradykinin receptors to phospholipase Cβ and β-adrenoceptors to adenylyl cyclase via G proteins. Upon receptor stimulation, the newly-formed cADPR may coordinately function to upregulate the release of Ca²⁺ from the type II ryanodine receptors as well as to facilitate Ca²⁺ influx through voltage-dependent Ca²⁺ channels. cADPR interacts with FK506, an immunosuppressant, at FKBP12.6, FK506-binding-protein, and calcineurin, or ryanodine receptors. cADPR also functions through activating calcineurin released from A-kinase anchoring protein (AKAP79). Thus, some G_q/11-coupled receptors can control cADPR-dependent modulation in Ca²⁺ signaling.