Journal
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
Volume 307, Issue 6, Pages C561-C570Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpcell.00080.2014
Keywords
purinergic inhibitory neurotransmission; colonic motility; smooth muscle layer
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Funding
- National Institute of Diabetes and Digestive and Kidney Diseases [R01 DK-091336]
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Enteric inhibitory neurotransmission is an important feature of the neural regulation of gastrointestinal motility. Purinergic neurotransmission, via P2Y(1) receptors, mediates one phase of inhibitory neural control. For decades, ATP has been assumed to be the purinergic neurotransmitter and smooth muscle cells (SMCs) have been considered the primary targets for inhibitory neurotransmission. Recent experiments have cast doubt on both of these assumptions and suggested that another cell type, platelet-derived growth factor receptor-alpha-positive (PDGFR alpha(+)) cells, is the target for purinergic neurotransmission. We compared responses of PDGFR alpha(+) cells and SMCs to several purine compounds to determine if these cells responded in a manner consistent with enteric inhibitory neurotransmission. ATP hyperpolarized PDGFR alpha(+) cells but depolarized SMCs. Only part of the ATP response in PDGFR alpha(+) cells was blocked by MRS 2500, a P2Y(1) antagonist. ADP, MRS 2365, beta-NAD, and adenosine 5-diphosphate-ribose, P2Y(1) agonists, hyperpolarized PDGFR alpha(+) cells, and these responses were blocked by MRS 2500. Adenosine 5-diphosphate-ribose was more potent in eliciting hyperpolarization responses than beta-NAD. P2Y(1) agonists failed to elicit responses in SMCs. Small hyperpolarization responses were elicited in SMCs by a small-conductance Ca2+-activated K+ channel agonist, cyclohexyl-[2-(3,5-dimethyl-pyrazol-1-yl)-6-methyl-pyrimidin-4-yl]-amine, consistent with the low expression and current density of small-conductance Ca2+-activated K+ channels in these cells. Large-amplitude hyperpolarization responses, elicited in PDGFR alpha(+) cells, but not SMCs, by P2Y(1) agonists are consistent with the generation of inhibitory junction potentials in intact muscles in response to purinergic neurotransmission. The responses of PDGFR alpha(+) cells and SMCs to purines suggest that SMCs are unlikely targets for purinergic neurotransmission in colonic muscles.
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