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The Effect of Protamine Sulfate on Gastric Acid Secretion and Histamine Release

魚精蛋白對胃酸分泌的作用與組織胺釋出之關連研究

摘要


測定大白鼠注射protamine sulfate 所導致的胃酸分泌增加量,發現反應增加量與注射劑量有相關性。同一隻大白鼠經注射兩protamine sulfate (20 mg/kg) 可導致幾乎相同的胃酸分泌增加量;故此種注射劑量尚不致於引起胃酸分泌之快速防禦反應(tachyphylaxis) 分析魚精蛋白注射(20mg/kg)所導致的胃酸分泌,發現2/3的大白鼠呈中等程度的酸分泌反應(2.5~8.5μEq),而少數個體產生較強反應(12.5μEq)。受檢的65隻大白鼠之胃酸分泌反應呈對數常態分佈。若由靜脈注射protamine sulfate前30分鐘先由腹腔各別注射cimetidine(2 mg/kg),或cromolyn sodium(10mg/kg)或atropine sulfate(5mg/kg)則可阻止protamine sulfate所引起之胃酸分泌。 測注射前後,血漿中histamine含量的變化,可發現protamine sulfate(30mg/kg)有意地增加血漿中histamine含量。 以pH-stat的方法對牛蛙胃黏膜離體組織測定胃分泌;此種刺激胃酸分泌的作用,對經過cimetidine(10-4g/ml)前處理的胃黏膜亦有同樣的效果;由漿膜面淬取液發現protamine sulfate使組織胺之釋出增加。 綜合120隻大白鼠及22個牛蛙胃黏膜離體組織的試驗,protamine sulfate確定可引起胃酸分泌。此種現象與組織胺的釋出有關。因為經由組織胺來促使胃酸分泌增加所須的histamine量很大,故protamine sulfate注射引起的其它副作用,也可能以此種產生組織胺的釋出為最重要的因素。

關鍵字

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並列摘要


1. Gastric acid secretion (GAS) of rats was dose-dependently increased by intravenous injection of 10-40 mg/kg protamine sulfate (PS). The frequency of occurrence vs. total acid output induced by each injection of PS (20 mg/kg) reavealed a statistical lognormal distribution in 65 rats. 2. Treatment with pyrilamine (5mg/kg, i.p.) or diphenhydramine (5 mg/kg, i.p.) 30 min before the injection of PS failed to inhibit the protamineinduced gastric secretion (PIGAS). However, atropine (5 mg/kg), cromolyn sodium (10mg/kg, i.p.) of cimetidine (2 mg/kg, i.p.) inhibited this effect. 3. Acid secretion and histamine-release from isolated bullfrog gastric mucosal preparations were measured in vitro by a recording pH stat and fluorometric asay. PS (2×10-4g/ml)increased GAS and histamine-release in a mucosal solution and serosal solution respectively. After the spontaneous secretion was decreased by treatment with cimetidine (1×10-4g/ml)and washed with serosal solution. Further application of PS restored acid secretion and histamine-release. 4. It is concluded that PS induces histamine-release (both in vivo and in vitro) from histamine-containing cells, basophil leucocytes and mast cells, and thereafter stimulates the acid secretion from parietal cells.

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