Tachykinin receptor subtypes in the isolated guinea pig heart and their role in mediating responses to neurokinin A.
Tachykinin receptor subtypes in the isolated guinea pig heart and their role in mediating responses to neurokinin A.
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发表时间：
2000-07
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通讯作者：
Y. Chang;D. Hoover;J. C. Hancock;F. M. Smith
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作者：
Y. Chang;D. Hoover;J. C. Hancock;F. M. Smith
选择性速激肽激动剂用于鉴定分离的灌注豚鼠心脏中特定速激肽受体亚型介导的心脏和冠状动脉反应。使用选择性激动剂的受体脱敏和选择性拮抗剂的阻断来确定特定亚型在产生对神经激肽A（NKA）的反应中的作用。剂量依赖性心脏和冠状动脉效应通过静脉推注<$Sar（9）、Met（O（2））（11）P物质（<$Sar（9）、Met（O（2））（11）SP）、GR 64349和<$MePhe（7）神经激肽B（<$MePhe（7）NKB）（分别为NK（1）、NK（2）和NK（3）受体的选择性激动剂）诱发。每种激动剂均引起心动过缓，但GR 64349最有效（32 nmol时心率降低34 +/- 4%，n = 8）。32 nmol GR 64349也显著增加心室收缩力和灌注压（分别为25 +/- 6和33 +/-4%）。<$Sar（9），Met（O（2））（11）SP是一种独特的具有降低心室收缩力和灌注压的高效力的物质。推注25 nmol NKA可降低心率（48 +/-2%，n = 51），增加收缩力（26 +/- 2%），对灌注压有双相影响（降低24 +/- 1%，随后增加9.2 +/- 1.4%）。用GR 64349脱敏或用NK（2）拮抗剂SR 48968治疗可使对NKA的心动过缓反应降低75%以上，并消除正性肌力反应。其余心动过缓通过NK（3）受体发生。脱敏治疗用FK 888阻断Sar（9）、Met（O（2））（11）SP或NK（1），可消除NKA的舒张冠脉作用，增强升压反应。它的结论是，三种速激肽受体亚型存在于豚鼠心脏，每一个都有助于NKA诱发的整体反应。
Selective tachykinin agonists were used to identify cardiac and coronary responses mediated by specific tachykinin receptor subtypes in isolated, perfused guinea pig hearts. Receptor desensitization with selective agonists and blockade with selective antagonists were used to determine the role of specific subtypes in generating responses to neurokinin A (NKA). Dose-dependent cardiac and coronary effects were evoked by bolus injections of ¿Sar(9), Met(O(2))(11)substance P (¿Sar(9),Met(O(2))(11)SP), GR64349, and ¿MePhe(7)neurokinin B (¿MePhe(7)NKB) (selective agonists for NK(1), NK(2), and NK(3) receptors, respectively). Each agonist caused bradycardia, but GR64349 was most effective (34 +/- 4% decrease in heart rate with 32 nmol, n = 8). Prominent increases in ventricular contractility and perfusion pressure also occurred with 32 nmol of GR64349 (25 +/- 6 and 33 +/- 4%, respectively). ¿Sar(9), Met(O(2))(11)SP was unique in having a high potency for decreasing ventricular contractility and perfusion pressure. Bolus injections of 25 nmol of NKA decreased rate (48 +/- 2%, n = 51), increased contractility (26 +/- 2%), and had biphasic effects on perfusion pressure (24 +/- 1% decrease followed by 9.2 +/- 1.4% increase). Desensitization with GR64349 or treatment with the NK(2) antagonist SR48968 reduced the bradycardic response to NKA by greater than 75% and eliminated the positive inotropic response. The remaining bradycardia occurred through NK(3) receptors. Desensitization with ¿Sar(9),Met(O(2))(11)SP or NK(1) blockade with FK888 eliminated the coronary relaxant action of NKA and enhanced the pressor response. It is concluded that three tachykinin receptor subtypes are present in the guinea pig heart and that each contributes to the overall response evoked by NKA.