Gorman Mark W, Ogimoto Kayoko, Savage Margaret V, Jacobson Kenneth A, Feigl Eric O
Department of Physiology and Biophysics, University of Washington School of Medicine, Box 357290, Seattle, WA 98195-7290, USA.
Am J Physiol Heart Circ Physiol. 2003 Sep;285(3):H1040-7. doi: 10.1152/ajpheart.00981.2002. Epub 2003 May 22.
The role of P1 receptors and P2Y1 receptors in coronary vasodilator responses to adenine nucleotides was examined in the isolated guinea pig heart. Bolus arterial injections of nucleotides were made in hearts perfused at constant pressure. Peak increase in flow was measured before and after addition of purinoceptor antagonists. Both the P1 receptor antagonist 8-(p-sulfophenyl)theophylline and adenosine deaminase inhibited adenosine vasodilation. AMP-induced vasodilation was inhibited by P1 receptor blockade but not by adenosine deaminase or by the selective P2Y1 antagonist N6-methyl-2'-deoxyadenosine 3',5'-bisphosphate (MRS 2179). ADP-induced vasodilation was moderately inhibited by P1 receptor blockade and greatly inhibited by combined P1 and P2Y1 blockade. ATP-induced vasodilation was antagonized by P1 blockade but not by adenosine deaminase. Addition of P2Y1 blockade to P1 blockade shifted the ATP dose-response curve further rightward. It is concluded that in this preparation ATP-induced vasodilation results primarily from AMP stimulation of P1 receptors, with a smaller component from ATP or ADP acting on P2Y1 receptors. ADP-induced vasodilation is largely due to P2Y1 receptors, with a smaller contribution by AMP or adenosine acting via P1 receptors. AMP responses are mediated solely by P1 receptors. Adenosine contributes very little to vasodilation resulting from bolus intracoronary injections of ATP, ADP, or AMP.
在离体豚鼠心脏中研究了P1受体和P2Y1受体在冠状动脉对腺嘌呤核苷酸血管舒张反应中的作用。在恒压灌注的心脏中进行核苷酸的动脉推注。在添加嘌呤受体拮抗剂之前和之后测量流量的峰值增加。P1受体拮抗剂8-（对磺基苯基）茶碱和腺苷脱氨酶均抑制腺苷介导的血管舒张。AMP诱导的血管舒张受到P1受体阻断的抑制，但不受腺苷脱氨酶或选择性P2Y1拮抗剂N6-甲基-2'-脱氧腺苷3'，5'-双磷酸酯（MRS 2179）的抑制。ADP诱导的血管舒张受到P1受体阻断的中度抑制，并受到P1和P2Y1联合阻断的极大抑制。ATP诱导的血管舒张受到P1阻断的拮抗，但不受腺苷脱氨酶的拮抗。在P1阻断基础上添加P2Y1阻断使ATP剂量反应曲线进一步右移。得出的结论是，在该制剂中，ATP诱导的血管舒张主要源于AMP对P1受体的刺激，较小部分源于ATP或ADP作用于P2Y1受体。ADP诱导的血管舒张很大程度上归因于P2Y1受体，AMP或腺苷通过P1受体发挥的作用较小。AMP反应仅由P1受体介导。腺苷对冠状动脉内推注ATP、ADP或AMP所导致的血管舒张贡献很小。
