Fujinuma S, Kamikawa Y, Shimo Y
Br J Pharmacol. 1985 Nov;86(3):619-25. doi: 10.1111/j.1476-5381.1985.tb08938.x.
To characterize the histamine receptors in the muscularis mucosae, the isotonic responsiveness of the isolated muscularis mucosae of the guinea-pig oesophagus to histamine receptor agonists and antagonists was examined in vitro. Histamine (0.1-100 microM) produced a concentration-dependent contraction of the muscularis mucosae (EC50 = 1.6 +/- 0.2 microM). The contractions were rapid in onset, sustained, reversible by washing and the preparation did not show tachyphylaxis. 2-Methylhistamine (2-MH), 2-pyridylethylamine (PEA) and 4-methylhistamine (4-MH) produced similar sustained contractions of the muscularis mucosae. The order of sensitivity was histamine greater than 2-MH greater than PEA greater than 4-MH. Impromidine (10-300 microM) and dimaprit (10-300 microM) caused no response in this tissue. The contractile responses to histamine, 2-MH, and PEA were competitively antagonized by diphenhydramine, and the pA2 values were almost the same (approximately 8.1). Cimetidine (100 microM) could not modify the contractile response to these agonists. The contractile response to histamine was slightly inhibited by tetrodotoxin (0.3 microM), atropine (1 microM), indomethacin (0.1-3 microM) or aspirin (30-300 microM), and the EC50 value was increased about 2-6 times by these drugs. When the preparation was incubated in Tyrode solution containing various calcium concentrations (0, 0.45, 0.9 and 1.8 mM), the concentration-response curve to histamine was shifted to the right and downward; the effect was inversely dependent on the calcium concentration, and in a calcium-free medium the response to histamine was abolished. Verapamil (1-10 microM) partially inhibited the contractile response to histamine. 7 The present results indicate that the contraction of the guinea-pig oesophageal muscularis mucosae to histamine is mediated mainly by a direct action on the smooth muscle and partly by indirect actions via the stimulation of either endogenous prostaglandin biosynthesis or intramural cholinergic nerves. The histamine receptors responsible for contractions of this tissue are probably mainly of the H,- subtype with H2-receptors having a negligible role.
为了表征黏膜肌层中的组胺受体，在体外研究了豚鼠食管分离的黏膜肌层对组胺受体激动剂和拮抗剂的等张反应性。组胺（0.1 - 100 μM）引起黏膜肌层浓度依赖性收缩（EC50 = 1.6 ± 0.2 μM）。收缩起效迅速、持续，冲洗后可逆，且标本未出现快速耐受性。2 - 甲基组胺（2 - MH）、2 - 吡啶乙胺（PEA）和4 - 甲基组胺（4 - MH）引起类似的黏膜肌层持续收缩。敏感性顺序为组胺＞2 - MH＞PEA＞4 - MH。英普咪定（10 - 300 μM）和二甲双咪（10 - 300 μM）在该组织中未引起反应。对组胺、2 - MH和PEA的收缩反应被苯海拉明竞争性拮抗，pA2值几乎相同（约8.1）。西咪替丁（100 μM）不能改变对这些激动剂的收缩反应。对组胺的收缩反应被河豚毒素（0.3 μM）、阿托品（1 μM）、吲哚美辛（0.1 - 3 μM）或阿司匹林（30 - 300 μM）轻微抑制，这些药物使EC50值增加约2 - 6倍。当标本在含有不同钙浓度（0、0.45、0.9和1.8 mM）的台氏液中孵育时，对组胺的浓度 - 反应曲线向右下方移动；该效应与钙浓度呈负相关，在无钙培养基中对组胺的反应消失。维拉帕米（1 - 10 μM）部分抑制对组胺的收缩反应。目前的结果表明，豚鼠食管黏膜肌层对组胺的收缩主要通过对平滑肌的直接作用介导，部分通过刺激内源性前列腺素生物合成或壁内胆碱能神经的间接作用介导。负责该组织收缩的组胺受体可能主要是H1 - 亚型，H2 - 受体的作用可忽略不计。
