P2X1 Receptor-Deficient Mice Establish the Native P2X Receptor and a P2Y6-Like Receptor in Arteries

doi:10.1124/mol.62.6.1438

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Vol. 62, Issue 6, 1438-1445, December 2002

P2X₁ Receptor-Deficient Mice Establish the Native P2X Receptor and a P2Y₆-Like Receptor in Arteries

Catherine Vial and Richard J. Evans

Department of Cell Physiology & Pharmacology, University of Leicester, Leicester, United Kingdom

The contribution of P2 receptors to vasoconstriction of mouse mesenteric arteries was determined using wild-type (WT) andP2X₁ receptor-deficient (KO) animals. $alpha$ , $beta$ -methylene ATP ( $alpha$ , $beta$ -meATP)and ATP evoked transient inward currents and constrictions ofWT mesenteric arteries. In contrast, $alpha$ , $beta$ -meATP (100 µM) and ATP(100 µM) failed to evoke responses in KO arteries from a rangeof vascular beds. Nerve stimulation (100 pulses at 10 Hz) evokedconstrictions of mesenteric arteries. For WT arteries, the P2receptor antagonist pyridoxalphosphate-6-azophenyl-2'-5'-disulfonate(PPADS) (30 µM) reduced the amplitude of response by ~50%; theresidual constriction was abolished by prazosin (0.1 µM). In KOmice, vasoconstriction induced by nerve stimulation was reducedin amplitude by ~50%, unaffected by PPADS, but was abolished byprazosin. ADP (1 mM) (a P2Y₁, P2Y₁₂, and P2Y₁₃ receptor agonist)was ineffective. Because ATP had no effect on mesenteric arterytone from KO mice, this rules out the contribution of P2Y₂ receptors.The P2Y₄ receptor agonist ITP also failed to contract mesentericarteries. However, UTP and UDP evoked sustained contractions ofmesenteric arteries with similar potency (EC₅₀ ~ 10 µM). Complementarystudies using reverse-transcriptase polymerase chain reactionshowed that mesenteric arteries express P2Y₁, P2Y₂, and P2Y₆ receptors.These results demonstrate that homomeric P2X₁ receptors underliethe artery smooth muscle P2X receptor phenotype and contribute~50% to sympathetic neurogenic vasoconstriction and indicate thepresence of a UTP- and UDP-sensitive P2Y₆-like receptor, but notvasoconstrictor P2Y₂ or P2Y₄ receptors, on mouse mesentericarteries.

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