ATP as a putative sensory mediator: activation of intrinsic sensory neurons of the myenteric plexus via P2X receptors Bertrand, P. P en_US Bornstein, J. C. en_US 2021-11-25T13:35:17Z 2021-11-25T13:35:17Z 2002 en_US
dc.description.abstract The mucosal terminals of sensory neurons intrinsic to the wall of the intestine are sensitive to the chemical environment within the lumen. Lumenal stimuli probably release sensory mediators from the mucosal epithelium, which then activate the nerve terminals indirectly. Here, we tested the idea that ATP activates intrinsic sensory nerve terminals in a way consistent with its being a sensory mediator. We made intracellular recordings from intrinsic sensory neurons located in the myenteric plexus [identified as AH neurons, which are neurons with a long-lasting afterhyperpolarization following the action potential (AP)], located within 1 mm of intact mucosa. Focal electrical stimulation of the mucosa was used to locate and map regions innervated by each neuron. Application of ATP (1-2 mM in the pressure pipette) to these regions elicited trains of APs that originated at the sensory terminals. ATP-gamma -S produced a similar response, but alpha ,beta -methylene ATP and 2-methylthio-ATP were only weakly active. The P2 receptor antagonist pyridoxalphosphate-6-azophenyl-2',5'-disulphonic acid (PPADS) (60 µM in the bath) abolished the APs evoked by ATP and ATP-gamma -S but spared similar responses evoked by 5-hydroxytryptamine (5-HT). Another P2 receptor antagonist suramin (100 µM in the bath) did not significantly change the number of APs evoked by ATP. Either ATP or alpha ,beta -methylene ATP desensitized the ATP-evoked APs; 50% recovery occurred after ~5 sec. The number of APs evoked by ATP was reduced, but not abolished, by the selective 5-HT3 receptor antagonist granisetron (1 µM in the bath). ATP was applied to the cell bodies of sensory neurons to investigate whether the cell bodies express the same P2X receptor as the terminals. ATP evoked a fast depolarization associated with a reduction in input resistance and a reversal potential of -11 mV. This depolarization was potentiated by suramin and blocked by PPADS. We conclude that activation of an atypical excitatory P2X receptor by ATP triggers AP generation in the mucosal processes of the sensory neurons; endogenous 5-HT release may also contribute to activation of the nerve terminals. A similar P2X receptor exists on the cell body of the sensory neuron. Together, these data are consistent with a role for ATP as a sensory mediator in gastrointestinal chemosensory transduction. en_US
dc.description.uri en_US
dc.identifier.issn 0270-6474 en_US
dc.language English
dc.language.iso EN en_US
dc.rights CC BY-NC-ND 3.0 en_US
dc.rights.uri en_US
dc.source Legacy MARC en_US
dc.title ATP as a putative sensory mediator: activation of intrinsic sensory neurons of the myenteric plexus via P2X receptors en_US
dc.type Journal Article en
dcterms.accessRights metadata only access
dspace.entity.type Publication en_US
unsw.relation.faculty Medicine & Health
unsw.relation.ispartofjournal Journal of Neuroscience en_US
unsw.relation.ispartofpagefrompageto 4767-4775 en_US
unsw.relation.ispartofvolume 22 en_US
unsw.relation.originalPublicationAffiliation Bertrand, P. P, Medical Sciences, Faculty of Medicine, UNSW en_US
unsw.relation.originalPublicationAffiliation Bornstein, J. C. en_US School of Medical Sciences *
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