title: Platelet-derived growth factor receptor-α-positive cells and not smooth muscle cells mediate purinergic hyperpolarization in murine colonic muscles.
abstract: Enteric inhibitory neurotransmission is an important feature of the neural regulation of gastrointestinal motility. Purinergic neurotransmission, via P2Y1 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-α-positive (PDGFRα(+)) cells, is the target for purinergic neurotransmission. We compared responses of PDGFRα(+) cells and SMCs to several purine compounds to determine if these cells responded in a manner consistent with enteric inhibitory neurotransmission. ATP hyperpolarized PDGFRα(+) cells but depolarized SMCs. Only part of the ATP response in PDGFRα(+) cells was blocked by MRS 2500, a P2Y1 antagonist. ADP, MRS 2365, β-NAD, and adenosine 5-diphosphate-ribose, P2Y1 agonists, hyperpolarized PDGFRα(+) cells, and these responses were blocked by MRS 2500. Adenosine 5-diphosphate-ribose was more potent in eliciting hyperpolarization responses than β-NAD. P2Y1 agonists failed to elicit responses in SMCs. Small hyperpolarization responses were elicited in SMCs by a small-conductance Ca(2+)-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 Ca(2+)-activated K(+) channels in these cells. Large-amplitude hyperpolarization responses, elicited in PDGFRα(+) cells, but not SMCs, by P2Y1 agonists are consistent with the generation of inhibitory junction potentials in intact muscles in response to purinergic neurotransmission. The responses of PDGFRα(+) cells and SMCs to purines suggest that SMCs are unlikely targets for purinergic neurotransmission in colonic muscles.
authors: Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, Nevada.
authors: Masaaki
authors: M
authors: Kurahashi
authors: Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, Nevada.
authors: Violeta
authors: V
authors: Mutafova-Yambolieva
authors: Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, Nevada.
authors: Sang Don
authors: SD
authors: Koh
authors: Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, Nevada ksanders@medicine.nevada.edu.
authors: Kenton M
authors: KM
authors: Sanders
mesh_terms: D000244:Adenosine Diphosphate / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D003106:Colon / Q000166:cytology / Q000187:drug effects / Q000294:innervation / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D008564:Membrane Potentials; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects / Q000294:innervation / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism*; D009433:Neural Inhibition; D018408:Patch-Clamp Techniques; D058912:Purinergic P2Y Receptor Agonists / Q000494:pharmacology; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics / Q000378:metabolism*; D058472:Receptors, Purinergic P2Y1 / Q000187:drug effects / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D051640:Small-Conductance Calcium-Activated Potassium Channels / Q000819:agonists / Q000378:metabolism
chemical_list: C496900:Kcnn3 protein, mouse; C546383:P2ry1 protein, mouse; D058912:Purinergic P2Y Receptor Agonists; D058472:Receptors, Purinergic P2Y1; D011993:Recombinant Fusion Proteins; D051640:Small-Conductance Calcium-Activated Potassium Channels; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D020796:Receptor, Platelet-Derived Growth Factor alpha
keywords: colonic motility; purinergic inhibitory neurotransmission; smooth muscle layer