RT Journal Article
SR Electronic
T1 P2X<sub>1</sub> Receptor-Deficient Mice Establish the Native P2X Receptor and a P2Y<sub>6</sub>-Like Receptor in Arteries
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 1438
OP 1445
DO 10.1124/mol.62.6.1438
VO 62
IS 6
A1 Catherine Vial
A1 Richard J. Evans
YR 2002
UL http://molpharm.aspetjournals.org/content/62/6/1438.abstract
AB The contribution of P2 receptors to vasoconstriction of mouse mesenteric arteries was determined using wild-type (WT) and P2X1 receptor-deficient (KO) animals. α,β-methylene ATP (α,β-meATP) and ATP evoked transient inward currents and constrictions of WT mesenteric arteries. In contrast, α,β-meATP (100 μM) and ATP (100 μM) failed to evoke responses in KO arteries from a range of vascular beds. Nerve stimulation (100 pulses at 10 Hz) evoked constrictions of mesenteric arteries. For WT arteries, the P2 receptor antagonist pyridoxalphosphate-6-azophenyl-2′-5′-disulfonate (PPADS) (30 μM) reduced the amplitude of response by ∼50%; the residual constriction was abolished by prazosin (0.1 μM). In KO mice, vasoconstriction induced by nerve stimulation was reduced in amplitude by ∼50%, unaffected by PPADS, but was abolished by prazosin. ADP (1 mM) (a P2Y1, P2Y12, and P2Y13receptor agonist) was ineffective. Because ATP had no effect on mesenteric artery tone from KO mice, this rules out the contribution of P2Y2 receptors. The P2Y4 receptor agonist ITP also failed to contract mesenteric arteries. However, UTP and UDP evoked sustained contractions of mesenteric arteries with similar potency (EC50 ∼ 10 μM). Complementary studies using reverse-transcriptase polymerase chain reaction showed that mesenteric arteries express P2Y1, P2Y2, and P2Y6 receptors. These results demonstrate that homomeric P2X1 receptors underlie the artery smooth muscle P2X receptor phenotype and contribute ∼50% to sympathetic neurogenic vasoconstriction and indicate the presence of a UTP- and UDP-sensitive P2Y6-like receptor, but not vasoconstrictor P2Y2 or P2Y4 receptors, on mouse mesenteric arteries.