Fig. 3

Intracellular signaling pathways leading to increased cyclic ADP-ribose formation. Phosphorylation (P) of ADP-ribosyl cyclase (pink) is mediated by several pathways. Nitric oxide (NO), cyclic GMP (cGMP), and protein kinase G (G-kinase); acetylcholine (ACh), nicotinic ACh receptors (nAChR); voltage-operated Ca²⁺ channels (VOCC), Ca²⁺ and protein kinase A (A-kinase); norepinephrine (NE), β adrenaline receptors (bAdR). Activation of CD38 by GTP-binding protein (G protein) and various types of receptors triggers formation of cADPR. cADPR opens Ca²⁺ release channels of ryanodine receptor type II or III (RyR) with another cofactor, Ca²⁺ (not shown). Mobilization of Ca²⁺ from microsomes of Ca²⁺ pools increases [Ca²⁺] _i , resulting in OT release (not shown)