Adenosine 5'-diphosphate-ribose is a neural regulator in primate and murine large intestine along with ß-NAD

Key points Normal gastrointestinal activity depends upon orderly movement of nutrients and wastes through the alimentary canal. These movements require coordinated contractions of the muscular wall and regulation by excitatory and inhibitory motor neurons of the enteric nervous system. We examined the nature of candidate purine neurotransmitters (ATP and beta-NAD) and their metabolites (ADP and ADP-ribose) and the effects of these compounds on electrical and mechanical responses of colonic muscles. After release, ATP and beta-NAD were rapidly degraded to ADP and ADP-ribose, suggesting that inhibitory neural responses may include actions of primary transmitters and metabolites. Metabolites of both neurotransmitter candidates elicited responses similar to responses to inhibitory nerve stimulation. However, only ADP-ribose had pharmacology that mimicked the effects of the endogenous inhibitory neurotransmitter. These results help us better understand neural regulation of colonic motility and provide new insights about how defects in neural responses might lead to motility disorders such as constipation.