566
Agents and Actions vol. 8/6 (1978) Birkh~iuser Verlag, Basel
Stimulation of Gastric Acid Secretion by Dimaprit in Unanesthetized Rats by HERMOD PETERSEN a n d MORTON I. GROSSMAN VA Wadsworth Hospital Center and UCLA School of Medicine, Los Angeles, California
Abstract In unanesthetized rats, dimaprit and histamine given by intravenous infusion were about equipotent in stimulating gastric acid secretion. The maximal rate of acid secretion in response to dimaprlt was significantly greater than to histamine but not significantly different from the response to pentagastrin. T h e effect o f d i m a p r i t , a h i g h l y specific h i s t a m i n e H 2 - r e c e p t o r a g o n i s t , o n g a s t r i c acid s e c r e t i o n h a s b e e n s t u d i e d in a n e s t h e t i z e d r a t s a n d c a t s [1] a n d in u n a n e s t h e t i z e d d o g s [1] a n d cats [2]. T h e p r e s e n t s t u d y c o m p a r e s d i m a p r i t w i t h h i s t a m i n e a n d p e n t a g a s t r i n as s t i m u l a n t s o f g a s t r i c acid s e c r e t i o n in u n a n e s t h e t i z e d rats. Materials and methods The study was performed in male Sprague-Dawley rats weighing 237 to 440 g (mean 294 g). The rats were operated upon under ether anesthesia. A stainless steel cannula, 6 mm in outer diameter, was placed in the squamous part of the stomach and led out through the midline abdominal incision, which was closed with a double layer of sutures. A polyethylene cannula (1 mm in outside diameter) was then placed in the right jugular vein and passed through a subcutaneous channel to the region of the right scapula. After operation the rats were kept lightly restrained in modified Bollman cages. From the time of operation they received a continuous intravenous infusion of 0.15 M NaC1. The infusion rate was 0.3 ml h -1 between tests and 1 ml h during tests (syringe infusion pump, model 975, Harvard Apparatus). When not being tested, the rats were allowed to drink freely Ringer solution with 5% glucose. The rats were first tested about 24 h after operation and only one test was performed per day. One hour before testing the gastric cannula was opened and the drinking bottles removed. The gastric juice was collected in graduated tubes placed below the rat. All tests included a 60 min basal period. Eighteen rats received stepwise increasing doses of histamine (as dihydrochloride) and dimaprit (as dihydro-
chloride). Seven of the 18 rats also received stepwise increasing doses of pentagastrin and were also tested with saline only as a control. Each dose of the stimulants was dissolved in saline and infused intravenously for 30 rain. The order of testing was randomized. The volume of gastric juice was measured to the nearest 50 ~tl. Acid concentration was determined by titration with 0.1 M NaOH to pH 7. Acid output is expressed as /zmol kg 1 body weight min -I. Differences between means were evaluated by the Student t-test for paired comparison. Results T h e acid r e s p o n s e s t o h i s t a m i n e a n d d i m a prit w e r e closely similar for t h e d o s e r a n g e 3.1 t o 25 # m o l k g -1 h -1 (Fig. I). H i g h e r d o s e s o f
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BASAL 3.1 6.3 12.5 25 50 100 200 HISTAMINE AND DIMAPRIT (pmol kg-lh"1) 7.8 15.6 31.3 62.5 125 260 PENTAGASTRIN (nmolkg'lh'l) Figure 1 Gastric acid secretion in response to intravenous infusion of graded doses of dimaprit, histamine, pentagastrin, or saline control in unanesthetized rats. Dimaprit and histamine were studied in 18 rats; 7 of these also received pentagastrin and saline.
Stimulation of Gastric Acid Secretion by Dimaprit in Unanesthetized Rats
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Agents and Actions vol. 8/6 (1978) Birkh~iuser Verlag, Basel
Stimulation of Gastric Acid Secretion by Dimaprit in Unanesthetized Rats by HERMOD PETERSEN a n d MORTON I. GROSSMAN VA Wadsworth Hospital Center and UCLA School of Medicine, Los Angeles, California
Abstract In unanesthetized rats, dimaprit and histamine given by intravenous infusion were about equipotent in stimulating gastric acid secretion. The maximal rate of acid secretion in response to dimaprlt was significantly greater than to histamine but not significantly different from the response to pentagastrin. T h e effect o f d i m a p r i t , a h i g h l y specific h i s t a m i n e H 2 - r e c e p t o r a g o n i s t , o n g a s t r i c acid s e c r e t i o n h a s b e e n s t u d i e d in a n e s t h e t i z e d r a t s a n d c a t s [1] a n d in u n a n e s t h e t i z e d d o g s [1] a n d cats [2]. T h e p r e s e n t s t u d y c o m p a r e s d i m a p r i t w i t h h i s t a m i n e a n d p e n t a g a s t r i n as s t i m u l a n t s o f g a s t r i c acid s e c r e t i o n in u n a n e s t h e t i z e d rats. Materials and methods The study was performed in male Sprague-Dawley rats weighing 237 to 440 g (mean 294 g). The rats were operated upon under ether anesthesia. A stainless steel cannula, 6 mm in outer diameter, was placed in the squamous part of the stomach and led out through the midline abdominal incision, which was closed with a double layer of sutures. A polyethylene cannula (1 mm in outside diameter) was then placed in the right jugular vein and passed through a subcutaneous channel to the region of the right scapula. After operation the rats were kept lightly restrained in modified Bollman cages. From the time of operation they received a continuous intravenous infusion of 0.15 M NaC1. The infusion rate was 0.3 ml h -1 between tests and 1 ml h during tests (syringe infusion pump, model 975, Harvard Apparatus). When not being tested, the rats were allowed to drink freely Ringer solution with 5% glucose. The rats were first tested about 24 h after operation and only one test was performed per day. One hour before testing the gastric cannula was opened and the drinking bottles removed. The gastric juice was collected in graduated tubes placed below the rat. All tests included a 60 min basal period. Eighteen rats received stepwise increasing doses of histamine (as dihydrochloride) and dimaprit (as dihydro-
chloride). Seven of the 18 rats also received stepwise increasing doses of pentagastrin and were also tested with saline only as a control. Each dose of the stimulants was dissolved in saline and infused intravenously for 30 rain. The order of testing was randomized. The volume of gastric juice was measured to the nearest 50 ~tl. Acid concentration was determined by titration with 0.1 M NaOH to pH 7. Acid output is expressed as /zmol kg 1 body weight min -I. Differences between means were evaluated by the Student t-test for paired comparison. Results T h e acid r e s p o n s e s t o h i s t a m i n e a n d d i m a prit w e r e closely similar for t h e d o s e r a n g e 3.1 t o 25 # m o l k g -1 h -1 (Fig. I). H i g h e r d o s e s o f
' 30 v
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N
T
A
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BASAL 3.1 6.3 12.5 25 50 100 200 HISTAMINE AND DIMAPRIT (pmol kg-lh"1) 7.8 15.6 31.3 62.5 125 260 PENTAGASTRIN (nmolkg'lh'l) Figure 1 Gastric acid secretion in response to intravenous infusion of graded doses of dimaprit, histamine, pentagastrin, or saline control in unanesthetized rats. Dimaprit and histamine were studied in 18 rats; 7 of these also received pentagastrin and saline.
Stimulation of Gastric Acid Secretion by Dimaprit in Unanesthetized Rats
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