Steinmetz M, Bierer S, Hollah P, Rahn K H, Schlatter E
Medizinische Poliklinik, Westfälische Wilhelms-Universität Münster, Germany.
J Pharmacol Exp Ther. 2000 Sep;294(3):1182-7.
In the accompanying article, we showed that AP5A displayed heterogenous vasoactive effects in rat resistance arteries. It induced a stable vasoconstriction in the superior epigastric artery (SEA) and a transient vasoconstriction in the mesenteric resistance artery (MrA). In the phenylephrine-precontracted MrA AP5A induced a marked vasorelaxation. In this study the noncompetitive inhibition of the AP5A-induced vasoconstriction with pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid was found to be significantly stronger in MrA than in SEA. The nonselective P2 purinoceptor antagonist suramin inhibited AP5A-induced vasoconstriction in MrA only. The vasoconstriction by the P2X purinoceptor agonist alpha,beta-methylene ATP was inhibited by with pyridoxal-phosphate-6-azophenyl-2',4'-disulfonic acid and suramin similarly to that induced by AP5A. Thus, the AP5A-induced vasoconstriction is due to P2X receptor activation, but two different P2X receptors seem to be operational in the two different vessels. The AP5A-induced vasorelaxation of phenylephrine-precontracted MrA was inhibited by the P2Y(1) receptor antagonist ADP3'5'. The vasorelaxation induced by ADPbetaS (P2Y(1) agonist) also was inhibited by ADP3'5'. These findings suggest that AP5A-induced vasorelaxation of MrA is caused by P2Y(1) receptor activation. The P1 (A(2)) receptor antagonist 3, 7-dimethyl-1-propargylxanthine only slightly inhibited AP5A-induced vasorelaxation at high concentrations. Adenosine and the A(2) receptor agonist CGS21680 failed to produce significant vasorelaxation. Therefore, vasorelaxation in MrA does not involve A(2) purinoceptor activation. AP5A-induced vasorelaxation was not inhibited by Ca(2+)- or ATP-dependent K(+) channel blockade with clotrimazole, apamin, or glibenclamide. These data indicate that vasoconstriction in MrA and SEA by AP5A is due to different P2X receptors, and vasorelaxation in precontracted MrA is due to P2Y(1) receptor activation.
在随附的文章中，我们表明AP5A在大鼠阻力动脉中表现出异质性血管活性作用。它在上腹壁动脉（SEA）中诱导稳定的血管收缩，在肠系膜阻力动脉（MrA）中诱导短暂的血管收缩。在去氧肾上腺素预收缩的MrA中，AP5A诱导明显的血管舒张。在本研究中，发现用磷酸吡哆醛-6-偶氮苯基-2',4'-二磺酸对AP5A诱导的血管收缩的非竞争性抑制在MrA中比在SEA中明显更强。非选择性P2嘌呤受体拮抗剂苏拉明仅抑制MrA中AP5A诱导的血管收缩。P2X嘌呤受体激动剂α,β-亚甲基ATP引起的血管收缩与AP5A诱导的血管收缩类似，被磷酸吡哆醛-6-偶氮苯基-2',4'-二磺酸和苏拉明抑制。因此，AP5A诱导的血管收缩是由于P2X受体激活，但两种不同的P2X受体似乎在两种不同的血管中起作用。AP5A对去氧肾上腺素预收缩的MrA的血管舒张作用被P2Y(1)受体拮抗剂ADP3'5'抑制。ADPβS（P2Y(1)激动剂）诱导的血管舒张也被ADP3'5'抑制。这些发现表明，AP5A诱导的MrA血管舒张是由P2Y(1)受体激活引起的。P1（A(2)）受体拮抗剂3,7-二甲基-1-丙炔基黄嘌呤在高浓度时仅轻微抑制AP5A诱导的血管舒张。腺苷和A(2)受体激动剂CGS21680未能产生明显的血管舒张。因此，MrA中的血管舒张不涉及A(2)嘌呤受体激活。AP5A诱导的血管舒张未被克霉唑、蜂毒明肽或格列本脲对钙或ATP依赖性钾通道的阻断所抑制。这些数据表明，AP5A在MrA和SEA中引起的血管收缩是由于不同的P2X受体，而去氧肾上腺素预收缩的MrA中的血管舒张是由于P2Y(1)受体激活。
