关于(15S)-15-甲基前列腺素E1对豚鼠离体自发搏动右心房的强效正性变时作用的进一步研究。

Further studies on the potent positive chronotropic effect of (15S)-15-methyl-prostaglandin E1 on the guinea-pig isolated spontaneously beating right atrium.

Serdar Soydan A, Ugur M, Yazar O, Türker R K

Department of Pharmacology, Faculty of Medicine, University of Ankara, Turkey.

Gen Pharmacol. 1992 Mar;23(2):187-91. doi: 10.1016/0306-3623(92)90007-7.

Abstract

15-Me-PGE1 (10(-14)-10(-11) M) elicited a concentration-dependent and long-lasting increase in heart rate without an effect on contractility of the isolated spontaneously beating guinea-pig right atria. 2. Noradrenaline, histamine and PGE1 produced a concentration-dependent increase in both heart rate and contractility with relatively higher concentrations. 3. beta-Adrenoceptor blocker propranolol and histamine H2-receptor blocker cimetidine inhibited the effects of noradrenaline and histamine respectively without altering the positive chronotropic effect of 15-Me-PGE1. 4. Prazosin and lidocaine partially inhibited the effect of 15-Me-PGE1, while reducing Na+ concentration in the medium to 50 mM almost completely inhibited the positive chronotropic effect of the analog. 5. Calcium channel blocker, nicardipine, decreased the positive chronotropic effect of 15-Me-PGE1 in a concentration-dependent manner. 6. These results were taken as an evidence for the specific and unique effect of 15-Me-PGE1 in the guinea-pig sinoatrial node interacting with Na+ and Ca2+ fluxes probably through their specific exchangers.

摘要

15-甲基前列腺素E1（10⁻¹⁴ - 10⁻¹¹ M）引起离体豚鼠右心房自发搏动心率浓度依赖性和持久的增加，而对其收缩性无影响。2. 去甲肾上腺素、组胺和前列腺素E1在相对较高浓度时使心率和收缩性产生浓度依赖性增加。3. β-肾上腺素受体阻滞剂普萘洛尔和组胺H2受体阻滞剂西咪替丁分别抑制去甲肾上腺素和组胺的作用，而不改变15-甲基前列腺素E1的正性变时作用。4. 哌唑嗪和利多卡因部分抑制15-甲基前列腺素E1的作用，而将培养基中Na⁺浓度降至50 mM几乎完全抑制该类似物的正性变时作用。5. 钙通道阻滞剂尼卡地平以浓度依赖性方式降低15-甲基前列腺素E1的正性变时作用。6. 这些结果被视为15-甲基前列腺素E1在豚鼠窦房结具有特异性和独特作用的证据，其可能通过特定交换体与Na⁺和Ca²⁺通量相互作用。