Pharmacological characterization of nucleotide P2Y receptors on endothelial cells of the mouse aorta
2005
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- Autor(en) / Beteiligte
- Titel
- Pharmacological characterization of nucleotide P2Y receptors on endothelial cells of the mouse aorta
- Ist Teil von
- British journal of pharmacology, 2005-09, Vol.146 (2), p.288-295
- Ort / Verlag
- Oxford, UK: Blackwell Publishing Ltd
- Erscheinungsjahr
- 2005
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Nucleotides regulate various effects including vascular tone. This study was aimed to characterize P2Y receptors on endothelial cells of the aorta of C57BL6 mice. Five adjacent segments (width 2 mm) of the thoracic aorta were mounted in organ baths to measure isometric force development. Nucleotides evoked complete (adenosine 5′ triphosphate (ATP), uridine 5′ triphosphate (UTP), uridine 5′ diphosphate (UDP); >90%) or partial (adenosine 5′ diphosphate (ADP)) relaxation of phenylephrine precontracted thoracic aortic rings of C57BL6 mice. Relaxation was abolished by removal of the endothelium and was strongly suppressed (>90%) by inhibitors of nitric oxide synthesis. The rank order of potency was: UDP∼UTP∼ADP>adenosine 5′‐[γ‐thio] triphosphate (ATPγS)>ATP, with respective pD2 values of 6.31, 6.24, 6.22, 5.82 and 5.40. These results are compatible with the presence of P2Y1 (ADP>ATP), P2Y2 or P2Y4 (ATP and UTP) and P2Y6 (UDP) receptors. P2Y4 receptors were not involved, since P2Y4‐deficient mice displayed unaltered responses to ATP and UTP. The purinergic receptor antagonist suramin exerted surmountable antagonism for all agonists. Its apparent pKb for ATP (4.53±0.07) was compatible with literature, but the pKb for UTP (5.19±0.03) was significantly higher. This discrepancy suggests that UTP activates supplementary non‐P2Y2 receptor subtype(s). Further, pyridoxal‐phosphate‐6‐azophenyl‐2′‐4′‐disulphonic acid (PPADS) showed surmountable (UTP, UDP), nonsurmountable (ADP) or no antagonism (ATP). Finally, 2′‐deoxy‐N6‐methyladenosine3′,5′‐bisphosphate (MRS2179) inhibited ADP‐evoked relaxation only. Taken together, these results point to the presence of functional P2Y1 (ADP), P2Y2 (ATP, UTP) and P2Y6 (UDP) receptors on murine aorta endothelial cells. The identity of the receptor(s) mediating the action of UTP is not fully clear and other P2Y subtypes might be involved in UTP‐evoked vasodilatation. British Journal of Pharmacology (2005) 146, 288–295. doi:10.1038/sj.bjp.0706326
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0007-1188eISSN: 1476-5381DOI: 10.1038/sj.bjp.0706326Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_1576272
- Format
- –
- Schlagworte
- Animals, aorta, Aorta, Thoracic - cytology, Aorta, Thoracic - drug effects, Binding, Competitive - drug effects, Biological and medical sciences, Dose-Response Relationship, Drug, Endothelial Cells - drug effects, In Vitro Techniques, Medical sciences, Mice, Mice, Inbred C57BL, Mice, Knockout, mouse, Muscle Contraction - drug effects, Muscle Relaxation - drug effects, Muscle, Smooth, Vascular - cytology, Muscle, Smooth, Vascular - drug effects, Nucleotides, Nucleotides - pharmacology, P2Y1, P2Y2, P2Y4, P2Y6, Pharmacology. Drug treatments, Purinergic P2 Receptor Agonists, Purinergic P2 Receptor Antagonists, Receptors, Purinergic P2 - drug effects, Receptors, Purinergic P2 - genetics, Receptors, Purinergic P2 - physiology, relaxation, Vasodilator Agents - pharmacology