title: P2Y(1) receptors mediate purinergic relaxation in the equine pelvic flexure.
abstract: In the equine large intestine, the knowledge of the basic mechanisms underlying motility function is crucial to properly treat motility disorders. P2Y1 receptors are responsible for mediating purinergic colonic relaxation in several species. In vitro experimental studies of the circular muscle from the equine pelvic flexure (n = 6) were performed to characterize inhibitory and excitatory neuromuscular transmission. Electrophysiological studies showed that electrical field stimulation (EFS) evoked biphasic inhibitory junction potentials (IJPs) in smooth muscle cells: a fast IJP (IJPf) followed by a sustained IJP (IJPs). IJPs was sensitive to L-NNA 1 mM (a nitric oxide synthase inhibitor) (P <0.01), while IJPf was abolished by MRS2500 1 µM (a P2Y1 receptor antagonist) (P <0.001). EFS (5 Hz for 2 min) in the organ bath inhibited rhythmic contractions to 3.0 ± 2.5% of basal area under the curve (P <0.0001). EFS under MRS2500 1 µM or L-NNA 1 mM incubation inhibited contractions to 6.0 ± 2.8% (P <0.05) and 24.4 ± 11.3% respectively (P <0.05). Combination of MRS2500 1 µM and L-NNA 1 mM completely reversed the EFS-induced inhibition of colonic motility. Non-nitrergic, non-purinergic conditions were used to reveal voltage-dependent EFS-induced contractions sensitive to atropine 1 µM (P <0.001) and, therefore, cholinergic. In conclusion, nerve-mediated relaxation and contraction in the equine pelvic flexure involve the same mechanisms as those observed in the human colon. P2Y1 receptors mediate purinergic relaxations and are potential targets for the treatment of equine colonic motor disorders.
authors.affiliation: Department of Cell Biology, Physiology and Immunology and Neuroscience Institute, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Mas
authors.affiliation: Department of Cell Biology, Physiology and Immunology and Neuroscience Institute, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: N
authors.initials: N
authors.lastname: Mañé
authors.affiliation: Department of Animal Medicine and Surgery, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: F
authors.initials: F
authors.lastname: Fernández
authors.affiliation: Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Barcelona, Spain.
authors.forename: D
authors.initials: D
authors.lastname: Gallego
authors.affiliation: Department of Animal Medicine and Surgery, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Pumarola
authors.affiliation: Department of Cell Biology, Physiology and Immunology and Neuroscience Institute, Universitat Autònoma de Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Barcelona, Spain. Electronic address: marcel.jimenez@uab.es.
authors.forename: M
authors.initials: M
authors.lastname: Jiménez
mesh_terms: D000818:Animals; D003106:Colon / Q000187:drug effects* / Q000502:physiology; D003838:Deoxyadenine Nucleotides / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005769:Gastrointestinal Motility / Q000187:drug effects*; D006736:Horses / Q000378:metabolism*; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D019335:Nitroarginine / Q000494:pharmacology*; D058921:Purinergic P2Y Receptor Antagonists / Q000378:metabolism*
chemical_list: C495475:2-iodo-N(6)-methyl-(N)-methanocarba-2'-deoxyadenosine-3',5'-bisphosphate; D003838:Deoxyadenine Nucleotides; D004791:Enzyme Inhibitors; D058921:Purinergic P2Y Receptor Antagonists; D019335:Nitroarginine
keywords: Colon; Equine; Nitric oxide; Purine; Relaxation; Smooth muscle