Clinical Science (1992) 82,433-438 (Printed in Great Britain)
433
Effect of acute and chronic administration of ethanol on the pancreatic exocrine response to cholecystokinin in rats fed different diets M. A. MANSO, H. A. GALLEGO and I.
DE DlOS
Departamento de Fisiologia y Farmacologia, Facultad de Biologia, Universidad de Salamanca, Salamanca, Spain (Received
30 July17 October I99 I; accepted 8 November I99 I )
1. The effects of a diet rich in protein and fat, compared with a control diet, with or without chronic ingestion of ethanol on the pancreatic response to cholecystokinin were studied in rats after a 7-month treatment period. The acute effects of intraduodenal administration of 20% (v/v) ethanol were also analysed under these experimental conditions. 2. Animals receiving a diet rich in protein and fat showed a greater percentage increase in pancreatic output in response to cholecystokinin. 3. Chronic ethanol consumption reduced the basal secretion of protein and amylase; and even though the response capacity to cholecystokinin (considered as the percentage secretion on cholecystokinin stimulation with respect to basal secretion) was maintained, this led to hormone-stimulated secretion being decreased in comparison with the animals receiving water. In contrast, a lack of inhibition of basal volume flow and flow after cholecystokinin stimulation was seen after long-term ingestion of ethanol. 4. Acute administration of ethanol generally depressed cholecystokinin-stimulated pancreatic secretion. 5. On stimulation with cholecystokinin, the diet rich in protein and fat combined with long-term ingestion of ethanol led to non-parallel changes in the release of pancreatic enzymes, since an increase in trypsin secretion and a decrease in amylase secretion occurred concomitantly.
INTRODUCTION Ethanol, both itz vivo and irz vitro, has been reported to affect the exocrine pancreas [ 1-51. However, the effect of ethanol on the pancreas has generally been studied without considering the possible co-effects of different diets, even though it has been suggested that dietary habits may modify the effects of ethanol [6, 71. Additionally, the varied effects of ethanol described often depend on the secretory status of the gland. In fact, it has
been reported that higher levels of ethanol slightly stimulate basal secretion but inhibit amylase secretion stimulated by secretagogues which mobilize cellular calcium, such as cholecystokinin (CCK) [8]. Furthermore, ethanol might be expected to affect pancreatic stimulus-secretion coupling in view of its well-documented influence on pancreatic phosphatidylinositols which play an important role in this coupling [9, 101. The effects of long-term ethanol feeding on the pancreatic response to CCK have not been studied in depth [ll-131 and, likewise, the acute effects of ethanol on CCK-stimulated pancreatic secretion in ethanol-fed animals has also received little attention [2, 14, 151. Since chronic ethanol ingestion induces adaptative changes in membranes that make them resistant to the disordering effect of ethanol [16], the present work was planned with a dual aim: (1)to analyse to what extent the pancreatic response to CCK is affected by chronic ethanol ingestion alone or in combination with different diets, and (2) to determine if the acute effect of intraduodenal perfusion of ethanol on pancreatic secretion stimulated by CCK depends on whether or not the animals are accustomed to chronic ingestion of ethanol, and to see if their diet modulates this.
MATERIALS AND METHODS Animals and treatments Male Wistar rats weighing about 200 g at the beginning of experiments were fed one of two types of diet: a control diet (protein, 10% of total content; fats, 4%; carbohydrates, 72%; cellulose, 4%; vitamin complement, 5%; mineral complement, 5%) and a diet rich in protein and fat (protein, 28%; fats, 18%; carbohydrates, 40%; cellulose, 4%; vitamin complement, 5%; mineral complement, 5%). For each diet the rats were randomly divided into two groups: one drinking water and the other drinking a 20% (v/v) ethanol solution ad libitum. There were four experimental groups: CW (animals fed the control diet and drinking water, n = 7), CEth (animals fed the control
Key words: cholecystokinin,diet, ethanol, pancreatic exocrine secretion. Abbreviation: CCK, cholecystokinin. Correspondence: Dr Manuel A. Manso, Departamento de Fisiologia y Farmacologia, Facultad de Biologia, Universidad de Salamanca, 37008 Salamanca, Spain.
M. A. Manso et al.
434
Table I . Mortality and food, drink and calorie intakes throughout the treatment. n =number of animals. Values are means ~ S E M Statistical . significance (analysis of variance followed by lowest significant difference test): *P (0.05, **P (0.0 I compared with C W tPc0.05, ttP(0.01 compared with CEth; :P
433
Effect of acute and chronic administration of ethanol on the pancreatic exocrine response to cholecystokinin in rats fed different diets M. A. MANSO, H. A. GALLEGO and I.
DE DlOS
Departamento de Fisiologia y Farmacologia, Facultad de Biologia, Universidad de Salamanca, Salamanca, Spain (Received
30 July17 October I99 I; accepted 8 November I99 I )
1. The effects of a diet rich in protein and fat, compared with a control diet, with or without chronic ingestion of ethanol on the pancreatic response to cholecystokinin were studied in rats after a 7-month treatment period. The acute effects of intraduodenal administration of 20% (v/v) ethanol were also analysed under these experimental conditions. 2. Animals receiving a diet rich in protein and fat showed a greater percentage increase in pancreatic output in response to cholecystokinin. 3. Chronic ethanol consumption reduced the basal secretion of protein and amylase; and even though the response capacity to cholecystokinin (considered as the percentage secretion on cholecystokinin stimulation with respect to basal secretion) was maintained, this led to hormone-stimulated secretion being decreased in comparison with the animals receiving water. In contrast, a lack of inhibition of basal volume flow and flow after cholecystokinin stimulation was seen after long-term ingestion of ethanol. 4. Acute administration of ethanol generally depressed cholecystokinin-stimulated pancreatic secretion. 5. On stimulation with cholecystokinin, the diet rich in protein and fat combined with long-term ingestion of ethanol led to non-parallel changes in the release of pancreatic enzymes, since an increase in trypsin secretion and a decrease in amylase secretion occurred concomitantly.
INTRODUCTION Ethanol, both itz vivo and irz vitro, has been reported to affect the exocrine pancreas [ 1-51. However, the effect of ethanol on the pancreas has generally been studied without considering the possible co-effects of different diets, even though it has been suggested that dietary habits may modify the effects of ethanol [6, 71. Additionally, the varied effects of ethanol described often depend on the secretory status of the gland. In fact, it has
been reported that higher levels of ethanol slightly stimulate basal secretion but inhibit amylase secretion stimulated by secretagogues which mobilize cellular calcium, such as cholecystokinin (CCK) [8]. Furthermore, ethanol might be expected to affect pancreatic stimulus-secretion coupling in view of its well-documented influence on pancreatic phosphatidylinositols which play an important role in this coupling [9, 101. The effects of long-term ethanol feeding on the pancreatic response to CCK have not been studied in depth [ll-131 and, likewise, the acute effects of ethanol on CCK-stimulated pancreatic secretion in ethanol-fed animals has also received little attention [2, 14, 151. Since chronic ethanol ingestion induces adaptative changes in membranes that make them resistant to the disordering effect of ethanol [16], the present work was planned with a dual aim: (1)to analyse to what extent the pancreatic response to CCK is affected by chronic ethanol ingestion alone or in combination with different diets, and (2) to determine if the acute effect of intraduodenal perfusion of ethanol on pancreatic secretion stimulated by CCK depends on whether or not the animals are accustomed to chronic ingestion of ethanol, and to see if their diet modulates this.
MATERIALS AND METHODS Animals and treatments Male Wistar rats weighing about 200 g at the beginning of experiments were fed one of two types of diet: a control diet (protein, 10% of total content; fats, 4%; carbohydrates, 72%; cellulose, 4%; vitamin complement, 5%; mineral complement, 5%) and a diet rich in protein and fat (protein, 28%; fats, 18%; carbohydrates, 40%; cellulose, 4%; vitamin complement, 5%; mineral complement, 5%). For each diet the rats were randomly divided into two groups: one drinking water and the other drinking a 20% (v/v) ethanol solution ad libitum. There were four experimental groups: CW (animals fed the control diet and drinking water, n = 7), CEth (animals fed the control
Key words: cholecystokinin,diet, ethanol, pancreatic exocrine secretion. Abbreviation: CCK, cholecystokinin. Correspondence: Dr Manuel A. Manso, Departamento de Fisiologia y Farmacologia, Facultad de Biologia, Universidad de Salamanca, 37008 Salamanca, Spain.
M. A. Manso et al.
434
Table I . Mortality and food, drink and calorie intakes throughout the treatment. n =number of animals. Values are means ~ S E M Statistical . significance (analysis of variance followed by lowest significant difference test): *P (0.05, **P (0.0 I compared with C W tPc0.05, ttP(0.01 compared with CEth; :P
