Zavecz J H, Yellin T O
Eur J Pharmacol. 1981 May 8;71(2-3):297-306. doi: 10.1016/0014-2999(81)90032-7.
We have investigated in the isolated, perfused guinea pig heart whether a alpha-adrenergic imidazolines, tolazoline and tetrahydrozoline stimulate histamine H2-receptors directly or via the release of endogenous histamine. At 30 degrees C neither tolazoline nor tetrahydrozoline released histamine. However, both increased heart rate, contractility, and decreased coronary vascular resistance as a function of dose. The H2-receptor antagonists cimetidine and tiotidine blocked the effects of tolazoline and tetrahydrozoline. The actions of tetrahydrozoline were confined to its 1-isomer. At 37 degrees C tolazoline, but not tetrahydrozoline, released histamine into the coronary perfusate. The maximum tolazoline-induced change in heart rate was 2.5-3.0 times greater than tetrahydrozoline's, in distinct contrast to their identical effect at 30 degrees C. All other responses to the two drugs were the same at 30 and 37 degrees C. Our results suggest that tolazoline and tetrahydrozoline directly stimulate histamine H2-receptors. Because of the differences in the structures of imidazolines and histamine, these findings have implications for the current hypothesis regarding histamine H2-receptor activation.
我们在离体灌注的豚鼠心脏中研究了α-肾上腺素能咪唑啉类药物（妥拉唑啉和四氢唑啉）是直接刺激组胺H2受体，还是通过释放内源性组胺来发挥作用。在30℃时，妥拉唑啉和四氢唑啉均未释放组胺。然而，二者均能使心率加快、心肌收缩力增强，并使冠状动脉血管阻力随剂量增加而降低。H2受体拮抗剂西咪替丁和替替丁可阻断妥拉唑啉和四氢唑啉的作用。四氢唑啉的作用仅限于其1-异构体。在37℃时，妥拉唑啉可使组胺释放到冠状动脉灌注液中，而四氢唑啉则不能。妥拉唑啉引起的心率最大变化比四氢唑啉大2.5 - 3.0倍，这与它们在30℃时的相同作用形成明显对比。在30℃和37℃时，对这两种药物的所有其他反应均相同。我们的结果表明，妥拉唑啉和四氢唑啉可直接刺激组胺H2受体。由于咪唑啉类药物和组胺结构不同，这些发现对目前关于组胺H2受体激活的假说具有重要意义。
