Mantelli L, Amerini S, Filippi S, Ledda F
Department of Pharmacology, University of Florence, Italy.
Neuropeptides. 1992 Nov;23(3):193-8. doi: 10.1016/0143-4179(92)90122-d.
In guinea-pig isolated left atria, electrically stimulated at 1 Hz, isoprenaline and calcitonin gene-related peptide (CGRP) induced a positive inotropic effect in the same concentration range (0.3-100 nM). The increase in contractile tension induced by both agonists was associated with a reduction in time to peak tension and relaxation time. However CGRP was more active than isoprenaline in reducing the time to peak; this effect was more evident when the bath temperature was reduced from 30 degrees to 24 degrees C. The positive inotropic effects of isoprenaline and CGRP were potentiated by forskolin (30 nM), a direct activator of adenylcyclase; on the other hand, cholera toxin (1 microgram/ml), which irreversibly ribosylates Gs protein, did not modify the effect of CGRP, while antagonizing the concentration-response curve for isoprenaline. It is concluded that the increase in atrial contractile tension produced by isoprenaline and CGRP are linked to the adenylcyclase system in a different manner.
在豚鼠离体左心房中,以1赫兹频率进行电刺激时,异丙肾上腺素和降钙素基因相关肽(CGRP)在相同浓度范围(0.3 - 100纳摩尔)内诱导出正性肌力作用。两种激动剂诱导的收缩张力增加与达到峰值张力的时间和舒张时间的缩短有关。然而,CGRP在缩短达到峰值的时间方面比异丙肾上腺素更有效;当浴温从30摄氏度降至24摄氏度时,这种效应更明显。异丙肾上腺素和CGRP的正性肌力作用可被福斯高林(30纳摩尔)增强,福斯高林是腺苷酸环化酶的直接激活剂;另一方面,霍乱毒素(1微克/毫升)可使Gs蛋白不可逆地核糖基化,它不改变CGRP的作用,却拮抗异丙肾上腺素的浓度 - 反应曲线。结论是,异丙肾上腺素和CGRP产生的心房收缩张力增加以不同方式与腺苷酸环化酶系统相关联。