Kim L E, Teste J F, Sercombe R, Oudart N
Arch Int Pharmacodyn Ther. 1986 Oct;283(2):282-94.
4-Methylhistamine relaxed potassium-constricted perfused rabbit middle cerebral arteries at low concentrations (3 X 10(-11) - 3 X 10(-8) M) and constricted them at high concentrations (3 X 10(-7) - 10(-4) M). The relaxation was antagonized by either cimetidine (3 X 10(-7) or 10(-6) M) or mepyramine (3 X 10(-8) M) given 20 min before testing a series of increasing concentrations of 4-methylhistamine, whereas the constriction was slightly potentiated by cimetidine and reversed by mepyramine. The reduction of relaxation was enhanced by a combination of both blockers. These results suggest the involvement of both H1- and H2-receptors in the 4-methylhistamine-induced relaxation. When dimaprit was compared with 4-methylhistamine, it acted only as a relaxing agent, not as a constricting agent. The dimaprit-induced relaxation was antagonized by either cimetidine (3 X 10(-7) M) or mepyramine (3 X 10(-8) M). The inhibition of relaxation was enhanced with a combination of both blockers. This supports the hypothesis that the dimaprit-induced relaxation in the rabbit cerebral artery is also mediated through both H1- and H2-receptors. The H1-agonists 2-methylhistamine and 2-pyridyl ethylamine induced two kinds of responses: an initial relaxation at low concentrations which was reversed by mepyramine (3 X 10(-8) or 10(-6) M) but not by cimetidine (10(-6) or 10(-5) M); this relaxation was followed at higher concentrations by a vasoconstriction which was antagonized by mepyramine (3 X 10(-8), 3 X 10(-7) or 10(-6) M) but not by cimetidine (10(-6) or 10(-5) M). Relaxation by these agents therefore seems to involve the participation of H1-receptors. The pharmacological effects of the histaminergic agonists and antagonists used could be explained by assuming that a distinction exists in the rabbit middle cerebral artery between the receptors concerned in H1-mediated relaxation and H1-mediated constriction.
4-甲基组胺在低浓度（3×10⁻¹¹ - 3×10⁻⁸M）时可使钾离子收缩的灌注兔大脑中动脉舒张，而在高浓度（3×10⁻⁷ - 10⁻⁴M）时则使其收缩。在测试一系列递增浓度的4-甲基组胺之前20分钟给予西咪替丁（3×10⁻⁷或10⁻⁶M）或美吡拉敏（3×10⁻⁸M），可拮抗其舒张作用，而西咪替丁可使收缩作用稍有增强，美吡拉敏则可使其逆转。两种阻断剂联合使用可增强舒张作用的减弱。这些结果提示H1和H2受体均参与了4-甲基组胺诱导的舒张作用。当将二甲双胍与4-甲基组胺进行比较时，二甲双胍仅作为一种舒张剂，而非收缩剂。二甲双胍诱导的舒张作用可被西咪替丁（3×10⁻⁷M）或美吡拉敏（3×10⁻⁸M）拮抗。两种阻断剂联合使用可增强舒张作用的抑制。这支持了二甲双胍诱导兔脑动脉舒张也通过H1和H2受体介导的假说。H1激动剂2-甲基组胺和2-吡啶乙胺可诱导两种反应：低浓度时最初的舒张作用可被美吡拉敏（3×10⁻⁸或10⁻⁶M）逆转，但不能被西咪替丁（10⁻⁶或10⁻⁵M）逆转；在较高浓度时随后出现血管收缩，可被美吡拉敏（3×10⁻⁸、3×10⁻⁷或10⁻⁶M）拮抗，但不能被西咪替丁（10⁻⁶或10⁻⁵M）拮抗。因此，这些药物的舒张作用似乎涉及H1受体的参与。假设兔大脑中动脉中H1介导的舒张和H1介导的收缩所涉及的受体存在差异，则所使用的组胺能激动剂和拮抗剂的药理作用可以得到解释。
