Purinergic Signalling in the Gut.

Abstract

The article will begin with the discovery of purinergic inhibitory neuromuscular transmission in the 1960s/1970s, the proposal for purinergic cotransmission in 1976 and the recognition that sympathetic nerves release adenosine 5'-triphosphate (ATP), noradrenaline and neuropeptide Y, while non-adrenergic, non-cholinergic inhibitory nerve cotransmitters are ATP, nitric oxide and vasoactive intestinal polypeptide in variable proportions in different regions of the gut. Later, purinergic synaptic transmission in the myenteric and submucosal plexuses was established and purinergic receptors expressed by both glial and interstitial cells. The focus will then be on purinergic mechanosensory transduction involving release of ATP from mucosal epithelial cells during distension to activate P2X3 receptors on submucosal sensory nerve endings. The responses of low threshold fibres mediate enteric reflex activity via intrinsic sensory nerves, while high threshold fibres initiate pain via extrinsic sensory nerves. Finally, the involvement of purinergic signalling in an animal model of colitis will be presented, showing that during distension there is increased ATP release, increased P2X3 receptor expression on calcitonin gene-related peptide-labelled sensory neurons and increased sensory nerve activity.