Hill S J, Young J M
Br J Pharmacol. 1980 Apr;68(4):687-96. doi: 10.1111/j.1476-5381.1980.tb10861.x.
1 The equilibrium dissociation constant, K(d), for mepyramine binding to a particulate fraction from rat brain, 9.1 nM, determined from inhibition of the binding of 1 nM [(3)H]-mepyramine, was distinctly higher than that, 0.83 nM, measured on an equivalent preparation from guinea-pig brain.2 In rat brain the dissociation constant for mepyramine, determined from the binding of [(3)H]-mepyramine sensitive to inhibition by 2 x 10(-6) M promethazine, was higher than the constant obtained from the inhibition of the binding of 1 nM [(3)H]-mepyramine by non-radioactive mepyramine. This suggests that the promethazine-sensitive binding of [(3)H]-mepyramine includes a lower affinity non-receptor component, which becomes apparent at higher concentrations of [(3)H]-mepyramine.3 In the guinea-pig the dissociation constant for mepyramine determined from inhibition of [(3)H]-mepyramine binding was in good agreement with the value obtained from inhibition of the contractile response of intestinal smooth muscle to histamine. No similar comparison was possible in the rat. Rat ileum was much less sensitive to histamine and the contraction produced was not inhibited by 10(-6) M mepyramine, indicating that it is not mediated by H(1)-receptors.4 Low levels of promethazine-sensitive [(3)H]-mepyramine binding were present in membrane fractions prepared from the longitudinal muscle from rat small intestine, but the characteristics of this binding suggest that it may be largely to lower affinity, non-receptor sites.5 Promethazine was practically equipotent as an inhibitor of [(3)H]-mepyramine binding in rat and guinea-pig brain. Chlorpheniramine showed stereospecificity in the rat as in the guinea-pig, although the potency of the (+)-isomer in the rat was only a tenth of that in the guinea-pig. Histamine had nearly the same IC(50) in both species.6 The evidence suggests that the high-affinity [(3)H]-mepyramine binding sites in rat brain can be described as H(1)-receptors, but that these differ structurally from H(1)-receptors in the guinea-pig.7 The regional distribution of [(3)H]-mepyramine binding in rat brain was not the same as that in guinea-pig brain, the most notable difference being the very much lower level in rat cerebellum compared to guinea-pig cerebellum.
美吡拉敏与大鼠脑微粒体部分结合的平衡解离常数K(d)为9.1 nM，该值由1 nM [³H] - 美吡拉敏结合抑制法测定得出，明显高于豚鼠脑同等制剂上测得的0.83 nM。
在大鼠脑中，由对2×10⁻⁶ M异丙嗪抑制敏感的[³H] - 美吡拉敏结合所测定的美吡拉敏解离常数，高于由非放射性美吡拉敏抑制1 nM [³H] - 美吡拉敏结合所得到的常数。这表明[³H] - 美吡拉敏对异丙嗪敏感的结合包括一个较低亲和力的非受体成分，该成分在较高浓度的[³H] - 美吡拉敏时变得明显。
在豚鼠中，由[³H] - 美吡拉敏结合抑制法测定的美吡拉敏解离常数，与由组胺引起的肠平滑肌收缩反应抑制法得到的值高度一致。在大鼠中无法进行类似比较。大鼠回肠对组胺的敏感性低得多，10⁻⁶ M美吡拉敏不能抑制其产生的收缩，表明该收缩不是由H₁受体介导的。
从大鼠小肠纵肌制备的膜部分中存在低水平的对异丙嗪敏感的[³H] - 美吡拉敏结合，但这种结合的特性表明它可能主要是与较低亲和力的非受体位点结合。
异丙嗪作为[³H] - 美吡拉敏结合抑制剂在大鼠和豚鼠脑中的效力几乎相同。氯苯那敏在大鼠中与在豚鼠中一样表现出立体特异性，尽管(+) - 异构体在大鼠中的效力仅为在豚鼠中的十分之一。组胺在两个物种中的IC₅₀几乎相同。
证据表明，大鼠脑中高亲和力的[³H] - 美吡拉敏结合位点可被描述为H₁受体，但这些受体在结构上与豚鼠中的H₁受体不同。
[³H] - 美吡拉敏在大鼠脑中的结合区域分布与在豚鼠脑中不同，最显著的差异是大鼠小脑与豚鼠小脑相比水平非常低。
