Wang W Z, Zhao R R, Wu B W, Jin X H, Zhu L, Hjalmarson A, Fu M L
Department of Physiology, Shanxi Medical University, Taiyuan, China.
Blood Press Suppl. 1996;3:25-7.
The effects of anti-peptide antibodies (Ab) against the second extracellular loop of human muscarinic receptor-2 on cardiac function in rats in vivo were studied. These effects were compared with those of the muscarinic receptor agonist, carbachol (Carb). It was shown that: (1) both Carb and Ab administered intravenously in the same doses of 0.4 nmol, 1.0 nmol, and 2.0 nmol were able to inhibit the maximal rate of rise of ventricular pressure (+dp/dt max) in a dose-dependent manner. (2) The isoproterenol (Iso)-induced increase in HR and +dp/dt max were also markedly inhibited by Carb and Ab. Administration of 1.0 nmol Carb decreased the Iso-stimulated increase of HR from 13.6 +/- 2.0 to 4.9 +/- 0.7% and decreased the increase of +dp/dt max from 27.9 +/- 3.2 to 4.8 +/- 0.6%, respectively; whereas Ab decreased the HR to 6.5 +/- 1.1% and +dp/dt max to 13.5 +/- 1.2%, respectively. (3) Both the inhibitory effects of Carb and Ab could be significantly blocked by atropine (1.4 nmol). These findings suggest that the Ab display a stimulatory muscarinic activity similar to Carb in inhibiting the cardiac function as evidenced by its negative chronotropic and inotropic effects.
研究了抗人毒蕈碱受体2第二细胞外环的抗肽抗体(Ab)对大鼠体内心脏功能的影响。将这些影响与毒蕈碱受体激动剂卡巴胆碱(Carb)的影响进行了比较。结果表明:(1)以0.4 nmol、1.0 nmol和2.0 nmol相同剂量静脉注射的Carb和Ab均能以剂量依赖的方式抑制心室压力最大上升速率(+dp/dt max)。(2)异丙肾上腺素(Iso)诱导的心率和+dp/dt max增加也被Carb和Ab显著抑制。给予1.0 nmol Carb分别将Iso刺激的心率增加从13.6±2.0%降至4.9±0.7%,并将+dp/dt max增加从27.9±3.2%降至4.8±0.6%;而Ab分别将心率降至6.5±1.1%,将+dp/dt max降至13.5±1.2%。(3)Carb和Ab的抑制作用均可被阿托品(1.4 nmol)显著阻断。这些发现表明,Ab在抑制心脏功能方面表现出与Carb相似的刺激性毒蕈碱活性,其负性变时和变力作用证明了这一点。