P2X(1) receptor-deficient mice establish the native P2X receptor and a P2Y6-like receptor in arteries.
The contribution of P2 receptors to vasoconstriction of mouse mesenteric arteries was determined using wild-type (WT) and P2X(1) receptor-deficient (KO) animals. alpha,beta-methylene ATP (alpha,beta-meATP) and ATP evoked transient inward currents and constrictions of WT mesenteric arteries. In contrast, alpha,beta-meATP (100 microM) and ATP (100 microM) 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 microM) reduced the amplitude of response by approximately 50%; the residual constriction was abolished by prazosin (0.1 microM). In KO mice, vasoconstriction induced by nerve stimulation was reduced in amplitude by approximately 50%, unaffected by PPADS, but was abolished by prazosin. ADP (1 mM) (a P2Y(1), P2Y(12), and P2Y(13) receptor agonist) was ineffective. Because ATP had no effect on mesenteric artery tone from KO mice, this rules out the contribution of P2Y(2) receptors. The P2Y(4) receptor agonist ITP also failed to contract mesenteric arteries. However, UTP and UDP evoked sustained contractions of mesenteric arteries with similar potency (EC(50) approximately 10 microM). Complementary studies using reverse-transcriptase polymerase chain reaction showed that mesenteric arteries express P2Y(1), P2Y(2), and P2Y(6) receptors. These results demonstrate that homomeric P2X(1) receptors underlie the artery smooth muscle P2X receptor phenotype and contribute approximately 50% to sympathetic neurogenic vasoconstriction and indicate the presence of a UTP- and UDP-sensitive P2Y(6)-like receptor, but not vasoconstrictor P2Y(2) or P2Y(4) receptors, on mouse mesenteric arteries.
Vial
Catherine
C
Department of Cell Physiology & Pharmacology, University of Leicester, Leicester, United Kingdom.
Evans
Richard J
RJ
D000818:Animals; D002118:Calcium / Q000378:metabolism; D066298:In Vitro Techniques; D008565:Membrane Proteins; D008638:Mesenteric Arteries / Q000502:physiology*; D051379:Mice; D018048:Receptors, Purinergic P2 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D058469:Receptors, Purinergic P2X; D058925:Receptors, Purinergic P2Y12; D014661:Vasoconstriction / Q000502:physiology*
D008565:Membrane Proteins; C548577:P2ry12 protein, mouse; D018048:Receptors, Purinergic P2; D058469:Receptors, Purinergic P2X; D058925:Receptors, Purinergic P2Y12; D002118:Calcium