Pharmacological characterization of uracil nucleotide-preferring P2Y receptors modulating intestinal motility: a study on mouse ileum.

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Abstract

We investigated the possible modulation of theintestinal contractility by uracil nucleotides (UTP andUDP), using as model the murine small intestine. Contractileactivity of a mouse ileum longitudinal muscle wasexamined in vitro as changes in isometric tension. Transcriptsencoding for uracil-sensitive receptors was investigatedby RT-PCR. UDP induced muscular contractions,sensitive to PPADS, suramin, or MRS 2578, P2Y6 receptorantagonist, and mimicked by PSB 0474, P2Y6-receptoragonist. UTP induced biphasic effects characterized by anearly inhibition of the spontaneous contractile activityfollowed by muscular contraction. UTP excitatory effectswere antagonized by PPADS, suramin, but not by MRS2578, whilst the inhibitory effects were antagonized byPPADS but not by suramin or MRS 2578. UTPγS, P2Y2/4receptor agonist but not 2-thio-UTP, P2Y2 receptor agonist,mimicked UTP effects. The inhibitory effects induced byUTP was abolished by ATP desensitization and increasedby extracellular acidification. UDP or UTP responses wereinsensitive to TTX, atropine, or L-NAME antagonized byU-73122, inhibitor of phospholipase C (PLC) and preservedin the presence of nifedipine or low Ca2+ solution.Transcripts encoding the uracil nucleotide-preferring receptorswere expressed in mouse ileum. Functional postjunctionaluracil-sensitive receptors are present in thelongitudinal muscle of the mouse ileum. Activation ofP2Y6 receptors induces muscular contraction, whilst activationof P2Y4 receptors leads to inhibition of thecontractile activity. Indeed, the presence of atypical UTPsensitivereceptors leading to muscular contraction issuggested. All uracil-sensitive receptors are linked to thePLC pathway.
Lingua originaleEnglish
pagine (da-a)275-285
Numero di pagine11
RivistaPurinergic Signalling
Volume8
Stato di pubblicazionePublished - 2012

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cellular and Molecular Neuroscience
  • Cell Biology

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