نقش گيرنده هاي آدرنرژيك و 2 D دوپامينرژيك در اثرات بروموكريپتين بر ترشح اسيد معده ناشي ازهيستامين در موش بزرگ سفيد آزمايشگاهي نر

Role of adrenoceptors and dopamine D2 receptors in the effects of bromocriptine on histamine -induced gastric acid secretion in male rat

ﺳﺎﺑﻘﻪ و ﻫﺪف: ﯾﮑﯽ از ﻣﻬﻢ ﺗﺮﯾﻦ ﻋﻮاﻣﻞ اﯾﺠﺎد زﺧﻢ ﮔﻮارﺷﯽ ﺗﺮﺷﺢ زﯾﺎد اﺳﯿﺪ ﻣﻌﺪه اﺳﺖ. دوﭘﺎﻣﯿﻦ و آﮔﻮﻧﯿﺴﺖ ﻫـﺎ ي آن داراي ﻧﻘﺶ ﺣﻔﺎﻇﺘﯽ در ﻣﻌﺪه ﻣﯽ ﺑﺎﺷﻨﺪ. در اﯾﻦ ﭘﮋوﻫﺶ ﻧﻘﺶ ﮔﯿﺮﻧﺪه ﻫﺎي آدرﻧﺮژﯾـ ﮏ و 2 D دوﭘﺎﻣﯿﻨﺮژﯾـ ﮏ در اﺛـﺮ ﺑﺮوﻣﻮﮐﺮﯾﭙﺘﯿﻦ ﺑﺮ ﺗﺮﺷﺢ ﺗﺤﺮﯾﮏ ﺷﺪه ي اﺳﯿﺪ ﻣﻌﺪه ﻧﺎﺷﯽ از ﻫﯿﺴﺘﺎﻣﯿﻦ ﻣﻮرد ارزﯾﺎﺑﯽ ﻗﺮار ﮔﺮﻓﺖ. ﻣﻮاد و روش ﻫﺎ: در اﯾﻦ ﻣﻄﺎﻟﻌﻪ از 93 ﺳﺮ ﻣﻮش ﺻﺤﺮاﯾﯽ ﻧﺮ ﻧﮋاد وﯾﺴﺘﺎر ﺑﺎ وزن 180 ﺗﺎ 200 ﮔﺮم اﺳﺘﻔﺎده ﺷﺪ. ﭘـﺲ از ﺑﯿﻬﻮﺷﯽ ﺑﺎ ﻣﺨﻠﻮط ﮐﺘﺎﻣﯿﻦ و زاﯾﻼزﯾﻦ، ورﯾﺪ ژوﮔﻮﻻر ﺟﻬﺖ اﻧﻔﻮزﯾﻮن ﻫﯿﺴﺘﺎﻣﯿﻦ و ﻧﺎي ﺟﻬﺖ ﺗﺮاﮐﺌﻮﺳﺘﻮﻣﯽ و ﺟﻠـﻮﮔ ﯿﺮي از ﺧﻔﻪ ﺷﺪن ﺣﯿﻮان در دﺳﺘﺮس ﻗﺮار ﮔﺮﻓﺖ. ﺟﻬﺖ ورود ﺳﺎﻟﯿﻦ ﻓﯿﺰﯾﻮﻟﻮژﯾﮏ و ﺧﺮوج ﺗﺮﺷﺤﺎت ﻣﻌﺪه ﺑـﻪ ﺗﺮﺗ ﯿـ ﺐ ﯾـ ﮏ ﮐﺎﻧﻮﻟﯽ ﭘﻠﯽ اﺗﯿﻠﻨﯽ از ﻃﺮﯾﻖ ﻣﺮي و ﯾﮏ ﻟﻮﻟﻪ ﭘﻠﯽ اﺗﯿﻠﻨﯽ از ﻣﺤﻞ اﺗﺼﺎل ﻣﻌﺪه دﺋﻮدﻧﻮم درون ﻣﻌﺪه ﻗـﺮار داده ﺷـﺪ . ﺑـﻪ ﻣﺪت 2 ﺳﺎﻋﺖ ﻫﺮ 10 دﻗﯿﻘﻪ 2ﻣﯿﻠﯽ ﻟﯿﺘﺮ ﺳﺎﻟﯿﻦ ﻓﯿﺰﯾﻮﻟﻮژﯾﮏ از ﻃﺮﯾﻖ ﻟﻮﻟﻪ ﻣﺮوي وارد و از ﻟﻮﻟﻪ ﻣﻌﺪي- دﺋﻮدﻧﻮﻣﯽ ﺧﺎرج و pH ﻣﺤﻠﻮل ﺳﻨﺠﯿﺪه، ﺑﺎ اﺳﺘﻔﺎده از ﺳﻮد 0/1 ﻧﺮﻣﺎل ﺗﯿﺘﺮ و ﻣﯿﺰان اﺳﯿﺪ ﺑﻪ ﺻﻮرت ﻣﯿﮑﺮواﮐﯽ واﻻن ﺑﻪ ازاي ﻫﺮ 10 دﻗﯿﻘﻪ ﮔﺰارش ﺷﺪ. ﯾﺎﻓﺘﻪ ﻫﺎ: اﻧﻔﻮزﯾﻮن ورﯾﺪي ﻫﯿﺴﺘﺎﻣﯿﻦ ﺑﻪ ﻣﯿﺰان mg/100g/h 0/8 ﻣﻨﺠﺮ ﺑﻪ اﻓﺰاﯾﺶ ﻣﻌﻨﯽ دار در ﺗﺮﺷـﺢ اﺳـﯿﺪ ﻣﻌـﺪه ﮔﺮدﯾﺪ ﮐﻪ در دﻗﯿﻘﻪ 30 ﺷﺮوع و ﺗﺎ ﭘﺎﯾﺎن آزﻣﺎﯾﺶ اداﻣﻪ ﯾﺎﻓﺖ. اﺳﺘﻔﺎده از ﺑﺮوﻣﻮﮐﺮﯾﭙﺘﯿﻦ (آﮔﻮﻧﯿﺴـﺖ ﮔﯿﺮﻧـﺪه ﻫـﺎي گيرنده 2 D دوپامين) mg/kg 8 ﻗﺒﻞ از اﻧﻔﻮزﯾﻮن ورﯾﺪي ﻫﯿﺴﺘﺎﻣﯿﻦ ﻣﻮﺟﺐ ﮐﺎﻫﺶ ﻣﻌﻨﯽ دار ﺗﺮﺷـﺢ اﺳـﯿﺪ ﻧﺎﺷـﯽ از ﻫﯿﺴـﺘﺎﻣﯿﻦ ﮔﺮدﯾﺪ. ﻫﻤﭽﻨﯿﻦ ﺗﺰرﯾﻖ دوﻣﭙﺮﯾﺪون (آﻧﺘﺎﮔﻮﻧﯿﺴﺖ ﻣﺤﯿﻄﯽ ﮔﯿﺮﻧﺪه ﻫﺎي 2 D) و ﭘﺮوﭘﺮاﻧﻮﻟﻮل (آﻧﺘﺎﮔﻮﻧﯿﺴﺖ ﮔﯿﺮﻧﺪه ﻫﺎي ﺑﺘﺎ آدرﻧﺮژﯾﮏ) ﻗﺒﻞ از ﺑﺮوﻣﻮﮐﺮﯾﭙﺘﯿﻦ اﺛﺮ ﺗﻀﻌﯿﻔﯽ ﺑﺮوﻣﻮﮐﺮﯾﭙﺘﯿﻦ ﺑﺮ ﺗﺮﺷﺢ اﺳﯿﺪ ﻧﺎﺷﯽ از ﻫﯿﺴﺘﺎﻣﯿﻦ را ﺑﻄـﻮر ﻣﻌﻨـ ﯽ داري ﺗﺸﺪﯾﺪ ﮐﺮد. ﻧﺘﯿﺠﻪ ﮔﯿﺮي: اﺛﺮ ﺑﺮوﻣﻮﮐﺮﯾﭙﺘﯿﻦ ﺑﺮ ﺗﺮﺷﺢ اﺳﯿﺪ ﻧﺎﺷﯽ از ﻫﯿﺴﺘﺎﻣﯿﻦ اﺣﺘﻤﺎﻻ از ﻃﺮﯾﻖ ﮔﯿﺮﻧﺪه ﻫﺎي دوﭘﺎﻣﯿﻨﯽ 2 D و ﺑﺘـﺎ آدرﻧﺮژﯾﮏ اﻋﻤﺎل ﻧﻤﯽ ﮔﺮدد.

Introduction: Gastric acid secretion is one of the most important causes of peptic ulcer. Dopamine and its agonists have a protective role in the stomach. In the present study the role of α1 and β adrenoceptors and dopamine D2 receptors in the effects of bromocriptine on histamine-induced gastric acid secretion were evaluated. Materials and Methods: 93 Male Wistar rats weighing between 180-220 g were used. After the induction of anesthesia with ketamine/xylazine, for histamine infusion and tracheostomy, jugular vein and trachea were exposed respectively. For injecting physiologic saline and removing gastric secretion a polyethylene tube and a cannula was inserted into the stomach through esophagus and pyloroduodenal junction respectively. Every 10 minute 2 milliliter Physiological saline was introduced and removed through esophagial and pyloro duodenal tube respectively during 2 hour period of experiment. pH of removed solution was detected, using 0.1 N NaOH was titrated and then acid content was reported as μEq/10 minute. Results: Gastric acid secretion was increased significantly 30 minute after histamine (0.8 mg/100g/h) infusion and remained high throughout experimental period. Administration of bromocriptine as a dopamine D2 receptor agonist (8 mg/kg) before histamine infusion significantly decreased stimulated gastric acid secretion. Domperidone (peripheral D2 receptor antagonist) and or propranolol (β adrenoceptor antagonist) injection before bromocriptine prominently augmented effect of bromocriptine on histaminestimulated gastric acid secretion. Conclusion: It is possible that effect of bromocriptine on histamine-stimulated gastric acid secretion does not mediated via D2 dopaminergic and β adrenergic receptors.