Hirschowitz B I, Hutchison G A
Am J Physiol. 1977 Sep;233(3):E225-8. doi: 10.1152/ajpendo.1977.233.3.E225.
H+ and pepsin output were studied in four gastric fistula dogs with histamine and in five dogs with 4-methylhistamine (4(Me)H), an H2 histamine receptor agonist with little H1 effect. Each amine was given in 45-min incremental step doses to constitute full dose-response curves. Pepsin output was biphasic with both drugs. Peak pepsin output occurred at low doses (less than or equal to 5 microgram/kg-h) and progressive inhibition of output was seen at higher doses, but H+ output was stimulated at all doses. The H2 receptor antagonist, cimetidine, competitively inhibited H+ stimulation. The pepsin response to histamine or 4(Me)H was converted to a positive logsigmoid response when cimetidine was given at the same time. In the presence of cimetidine (1 mg/kg-h), the outputs of H+ and pepsin were positively correlated in the full histamine dose range. These data show that histamine effects on pepsin secretin are a mixture of stimulation and inhibition and that the receptor responsible for pepsin stimulation is of a high affinity, low Km, H2 type, whereas inhibition at high doses of histamine is probably mediated by a low affinity, high Km receptor, also H2 type.
在4只具有胃瘘的犬中研究了组胺对氢离子（H⁺）和胃蛋白酶分泌的影响，并在5只犬中研究了4-甲基组胺（4(Me)H）的作用，4-甲基组胺是一种几乎无H₁效应的H₂组胺受体激动剂。以45分钟递增的阶梯剂量给予每种胺类药物，以构建完整的剂量-反应曲线。两种药物均可使胃蛋白酶分泌呈双相变化。胃蛋白酶分泌峰值出现在低剂量（小于或等于5微克/千克·小时）时，高剂量时胃蛋白酶分泌逐渐受到抑制，但所有剂量均能刺激H⁺分泌。H₂受体拮抗剂西咪替丁竞争性抑制H⁺的刺激作用。当同时给予西咪替丁时，胃蛋白酶对组胺或4(Me)H的反应转变为正对数S形反应。在存在西咪替丁（1毫克/千克·小时）的情况下，在组胺的整个剂量范围内，H⁺和胃蛋白酶的分泌呈正相关。这些数据表明，组胺对胃蛋白酶分泌的作用是刺激和抑制的混合作用，负责胃蛋白酶刺激的受体是高亲和力、低Km的H₂型受体，而高剂量组胺的抑制作用可能是由低亲和力、高Km的受体介导的，也是H₂型受体。
