用苯氧苄胺阻断豚鼠离体回肠中激动剂产生的收缩反应。
Blockade by phenoxybenzamine of the contractor response produced by agonists in the isolated ileum of the guinea-pig.
作者信息
Cook D A
出版信息
Br J Pharmacol. 1971 Sep;43(1):197-209. doi: 10.1111/j.1476-5381.1971.tb07169.x.
Abstract
- The effects of various concentrations of phenoxybenzamine (dibenzyline) on the contractor response of the isolated ileum of the guinea-pig were investigated. The agonists tested were histamine, 5-hydroxytryptamine (5-HT), acetycholine and potassium chloride.2. In addition, uptake of (14)C-phenoxybenzamine into the ileum was determined as a function of antagonist concentration. The uptake increases sharply at concentrations above 10(-6) g/ml, (3x10(-6)M) and was not saturable at any concentration tested.3. In the presence of low concentrations of phenoxybenzamine, the dose-response curve for histamine undergoes a parallel shift of about 0.5 log units. At higher concentrations of phenoxybenzamine the maximum response is depressed. In the case of the other agonists, the maximum response is depressed as soon as any blockade becomes apparent.4. The ease of blockade with phenoxybenzamine is 5-HT >/= histamine>> acetylcholine >/= potassium chloride.5. These results do not lend support to the ;spare-receptor' hypothesis and may be better explained by the ;two-site' hypothesis of Moran & Triggle (1970).6. It may further be concluded that the successful antagonism of potassium-induced contractions in this preparation lies in the ability of phenoxybenzamine to prevent the action of released acetylcholine. In the case of the contraction induced by 5-HT, phenoxybenzamine probably interferes with the 5-HT receptor responsible for neuronal release of acetycholine.
摘要
研究了不同浓度的酚苄明（双苄胺）对豚鼠离体回肠收缩反应的影响。所测试的激动剂有组胺、5-羟色胺（5-HT）、乙酰胆碱和氯化钾。
此外，测定了（14）C-酚苄明在回肠中的摄取量与拮抗剂浓度的关系。在浓度高于10（-6）g/ml（3×10（-6）M）时摄取量急剧增加，且在所测试的任何浓度下均未达到饱和。
在低浓度酚苄明存在时，组胺的剂量-反应曲线发生约0.5对数单位的平行位移。在较高浓度的酚苄明作用下，最大反应受到抑制。对于其他激动剂，一旦出现任何阻断作用，最大反应就会受到抑制。
酚苄明阻断作用的难易程度为5-HT≥组胺>>乙酰胆碱≥氯化钾。
这些结果不支持“备用受体”假说，而用莫兰和特里格尔（1970年）的“双位点”假说可能能更好地解释。
还可以进一步得出结论，在该制剂中成功拮抗钾诱导的收缩作用在于酚苄明能够阻止释放的乙酰胆碱发挥作用。对于5-HT诱导的收缩，酚苄明可能干扰负责乙酰胆碱神经元释放的5-HT受体。
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