Dataset Information

Novel vasocontractile role of the P2Y₁₄ receptor: characterization of its signalling in porcine isolated pancreatic arteries.

ABSTRACT:

Background and purpose

The P2Y₁₄ receptor is the newest member of the P2Y receptor family; it is G(i/o) protein-coupled and is activated by UDP and selectively by UDP-glucose and MRS2690 (2-thiouridine-5'-diphosphoglucose) (7-10-fold more potent than UDP-glucose). This study investigated whether P2Y₁₄ receptors were functionally expressed in porcine isolated pancreatic arteries.

Experimental approach

Pancreatic arteries were prepared for isometric tension recording and UDP-glucose, UDP and MRS2690 were applied cumulatively after preconstriction with U46619, a TxA₂ mimetic. Levels of phosphorylated myosin light chain 2 (MLC2) were assessed with Western blotting. cAMP concentrations were assessed using a competitive enzyme immunoassay kit.

Key results

Concentration-dependent contractions with a rank order of potency of MRS2690 (10-fold) > UDP-glucose ≥ UDP were recorded. These contractions were reduced by PPTN {4-[4-(piperidin-4-yl)phenyl]-7-[4-(trifluoromethyl)phenyl]-2-naphthoic acid}, a selective antagonist of P2Y₁₄ receptors, which did not affect responses to UTP. Contraction to UDP-glucose was not affected by MRS2578, a P2Y₆ receptor selective antagonist. Raising cAMP levels and forskolin, in the presence of U46619, enhanced contractions to UDP-glucose. In addition, UDP-glucose and MRS2690 inhibited forskolin-stimulated cAMP levels. Removal of the endothelium and inhibition of endothelium-derived contractile agents (TxA₂, PGF(2α) and endothelin-1) inhibited contractions to UDP glucose. Y-27632, nifedipine and thapsigargin also reduced contractions to the agonists. UDP-glucose and MRS2690 increased MLC2 phosphorylation, which was blocked by PPTN.

Conclusions and implications

P2Y₁₄ receptors play a novel vasocontractile role in porcine pancreatic arteries, mediating contraction via cAMP-dependent mechanisms, elevation of intracellular Ca²⁺ levels, activation of RhoA/ROCK signalling and MLC2, along with release of TxA₂, PGF(2α) and endothelin-1.

SUBMITTER: Alsaqati M

PROVIDER: S-EPMC3969082 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature

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Publications

Novel vasocontractile role of the P2Y₁₄ receptor: characterization of its signalling in porcine isolated pancreatic arteries.

Alsaqati M M Latif M L ML Chan S L F SL Ralevic V V

British journal of pharmacology 20140201 3

<h4>Background and purpose</h4>The P2Y₁₄ receptor is the newest member of the P2Y receptor family; it is G(i/o) protein-coupled and is activated by UDP and selectively by UDP-glucose and MRS2690 (2-thiouridine-5'-diphosphoglucose) (7-10-fold more potent than UDP-glucose). This study investigated whether P2Y₁₄ receptors were functionally expressed in porcine isolated pancreatic arteries.<h4>Experimental approach</h4>Pancreatic arteries were prepared for isometric tension recording and UDP-glucose ...[more]

PMID: 24138077

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Dataset Information

Novel vasocontractile role of the P2Y₁₄ receptor: characterization of its signalling in porcine isolated pancreatic arteries.

Background and purpose

Experimental approach

Key results

Conclusions and implications

Publications

Novel vasocontractile role of the P2Y₁₄ receptor: characterization of its signalling in porcine isolated pancreatic arteries.

Similar Datasets

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