Figure 2

A. Schematic representation of hypothesis for purinergic mechanosensory transduction in tubes (e.g., ureter, vagina, salivary and bile ducts, gut) and sacs (e.g., urinary and gall bladders, lung). It is proposed that distension leads to release of ATP from epithelium lining the tube or sac, which then acts on P2X₃ and/or P2X_2/3 receptors on subepithelial sensory nerves to convey sensory/nociceptive information to the CNS. (Reproduced from [5], with permission from Blackwell.) B. schematic of a novel hypothesis about purinergic mechanosensory transduction in the gut. It is proposed that ATP released from mucosal epithelial cells during moderate distension acts preferentially on P2X₃ and/or P2X_2/3 receptors on low-threshold subepithelial intrinsic sensory nerve fibers (labelled with calbindin) to modulate peristaltic reflexes. ATP released during extreme (colic) distension also acts on P2X₃ and/or P2X_2/3 receptors on high-threshold extrinsic sensory nerve fibers [labelled with isolectin B4 (IB4) or are peptidergic] that send messages via the dorsal root ganglia (DRG) to pain centres in the CNS. (Reproduced and modified from [115], published by John Wiley and Sons, Inc.)