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

Content Provider	Springer Nature Link
Author	Zizzo, Maria Grazia Mastropaolo, Mariangela Grählert, Jasmin Mulè, Flavia Serio, Rosa
Copyright Year	2011
Abstract	We investigated the possible modulation of the intestinal contractility by uracil nucleotides (UTP and UDP), using as model the murine small intestine. Contractile activity of a mouse ileum longitudinal muscle was examined in vitro as changes in isometric tension. Transcripts encoding for uracil-sensitive receptors was investigated by RT-PCR. UDP induced muscular contractions, sensitive to PPADS, suramin, or MRS 2578, P2Y$_{6}$ receptor antagonist, and mimicked by PSB 0474, P2Y$_{6}$-receptor agonist. UTP induced biphasic effects characterized by an early inhibition of the spontaneous contractile activity followed by muscular contraction. UTP excitatory effects were antagonized by PPADS, suramin, but not by MRS 2578, whilst the inhibitory effects were antagonized by PPADS but not by suramin or MRS 2578. UTPγS, P2Y$_{2}$/$_{4}$ receptor agonist but not 2-thio-UTP, P2Y$_{2}$ receptor agonist, mimicked UTP effects. The inhibitory effects induced by UTP was abolished by ATP desensitization and increased by extracellular acidification. UDP or UTP responses were insensitive to TTX, atropine, or L-NAME antagonized by U-73122, inhibitor of phospholipase C (PLC) and preserved in the presence of nifedipine or low Ca$^{2+}$ solution. Transcripts encoding the uracil nucleotide-preferring receptors were expressed in mouse ileum. Functional postjunctional uracil-sensitive receptors are present in the longitudinal muscle of the mouse ileum. Activation of P2Y$_{6}$ receptors induces muscular contraction, whilst activation of P2Y$_{4}$ receptors leads to inhibition of the contractile activity. Indeed, the presence of atypical UTP-sensitive receptors leading to muscular contraction is suggested. All uracil-sensitive receptors are linked to the PLC pathway.
Starting Page	275
Ending Page	285
Page Count	11
File Format	PDF
ISSN	15739538
Journal	Purinergic Signalling
Volume Number	8
Issue Number	2
e-ISSN	15739546
Language	English
Publisher	Springer Netherlands
Publisher Date	2011-11-20
Publisher Institution	International Purine Club
Publisher Place	Dordrecht
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	UDP UTP P2Y$_{2}$ receptors P2Y$_{4}$ receptors P2Y$_{6}$ receptors Intestinal motility Neurosciences Human Physiology Biomedicine general Cancer Research Pharmacology/Toxicology
Content Type	Text
Resource Type	Article
Subject	Cell Biology Molecular Biology Cellular and Molecular Neuroscience

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