ADP-ribosyl cyclase coupled with receptors via G proteins

Crude cell membranes in mammalian cells contain ADP-ribosyl cyclase, which converts NAD+ to cyclic ADP-ribose. Acetylcholine either increases or inhibits this activity in NG108-15 neuronal cells and adrenal chromaffin cells in a muscarinic receptor subtype-specific manner. Activation or inhibition of the cyclase activity is mimicked by GTP and blocked by bacterial toxins. These findings suggest that hormone or neurotransmitter receptors utilize the direct signaling pathway to ADP-ribosyl cyclase via G proteins within cell membranes, analogous to the previously established transduction pathways to adenylyl cyclase and phospholipase Cbeta.