Digestion 14: 364 -367 (1976)
Serum Gastrin Concentration after Sham Feeding and Feeding under the Influence of Propranolol in Man H. Kaess, H. Fänger, U. Teckentrup and M. Dörner Department of Internal Medicine, University of Heidelberg, Heidelberg and V. Medical Department, Krankenhaus München-Schwabing, Munich
Key Words. Adrenergic (3-receptor blocker • Feeding behavior • Gastrin Abstract. The influence of propranolol, 50 Mg/kg administered intravenously, on the gastrin concentration during sham feeding and after a test meal was studied in eight normal subjects. ^-Adrenergic blockade had no inhibitory effect on the gastrin response to feeding. Sham feeding did not provoke a significant rise of serum gastrin concentration; however, in three subjects a definite gastrin response occurred in the presence of (S-adrenergic blockade.
Recently it has been shown that the gastrin release after insulin hypogly cemia in man does not result from cholinergic, but from adrenergic stimulation (3—9). (3-Adrenergic blockade with propranolol provokes a small decrease of basal gastrin concentration and abolishes the gastrin response to insulin (3). Since the hypothesis of nervous intermediation by cholinergic impulses for gastrin release after feeding was not yet established in man (12), it seemed worth while to investigate the behavior of serum gastrin in response to a test meal under the influence of (3-adrenergic blockade.
Materials and Methods The study was performed in eight male volunteers aged between 20 and 30 years. After a rest period of 30 min 50 Mg/kg propranolol (Dociton®) or 10 ml 0.9% saline in the control series, were administered intravenously. After 15 min, sham feeding was performed for a period of 30 min. Then the subjects received a test meal for a 15-ntin period. The experiments were terminated after a subsequent observation period of 120 min. The order of the test was randomized. During the experiment venous blood samples were collected through a catheter, placed in a antecubital vein. Pulse rate and arterial blood pressure were noted. Serum specimens
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/6/2018 10:46:56 AM
Received: January 5, 1976; accepted: March 16, 1976.
Kaess/Fànger/Teckentmp/Dorner
365
were stored at 20 °C until gastrin was determined (3). All samples of a single subject were tested in the same assay. The intra-assay variance was 10% and the interassay 15%. The meal included 150g sirloin steak, boiled potatoes with butter (25 g) and mineral water (200 ml). For sham feeding the subjects were only allowed to see and to smell the freshly prepared test meal. The results are presented as means and standard errors of the mean. Student test for unpaired values was used for calculation of p values. The integrated response of gastrin was calculated as described previously (1. 3). The gastrin concentrations after starting the test meal were compared with mean basal gastrin concentration.
Results In the control series the serum gastrin concentration remained unchanged during sham feeding (fig. 1). After the meal the gastrin concentration in creased significantly from 75 to 99 pg/ml at 45 min (p < 0.01) and decreased slowly to 89 pg/ml at the end of the experiment. In the test series serum gastrin decreased from 75 to 70 pg/ml (p < 0.05) after administration of propranolol. During sham feeding the rise of gastrin from 70 to 80 pg/ml was not significant. Feeding resulted in a sustained gastrin response which did not differ significantly from the gastrin rise in the control experiments. The analysis of the results during sham feeding shows a rise of gastrin concentration above the mean basal concentration in one subject of the control series (15 %) and in three subjects in the propranolol series (28. 30 and 48 %).
Fig. 1. Serum gastrin concentration after sham feeding and feeding under the effect of propranolol (50 jug/kg) intravenously.
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/6/2018 10:46:56 AM
m in
Kaess /Fänger/Teckentrup/Dörner
366
6
5 A
Control
Propranolol
Fig. 2. Integrated gastrin response to feeding (ng/2 hi.
The integrated gastrin output after the test meal was 1.9 ng/2 h and 2.9 ng/2 h in the experiments performed under the influence of propranolol (fig. 2). The pulse rate was significantly lower after propranolol than in the control experiments.
Discussion
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/6/2018 10:46:56 AM
The present study indicates that the rise of serum gastrin following a test meal is not inhibited by propranolol. This result is in contrast to the behavior of gastrin after insulin hypoglycemia under the influence of (3-adrenergic blockade with this substance (3). Under these conditions a small decrease of basal gastrin and suppression of the gastrin response occurred, associated with a decrease of the HC1 secretion. Contradictory findings of previous authors, who had reported an unchanged gastrin response to insulin after 20 mg propranolol given orally, must be related to the different dosage and the route of administration of the drug (2, 5). A single oral dose of propranolol below 30 mg is completely extracted from the liver by high tissue affinity binding (8). Therefore, the unchanged gastrin re sponse to feeding after 40 mg propranolol orally, reported recently by Kronborg (4) is not enequivocal. In the present study the rise of gastrin, which occurs under (3-adrenergic blockade, with intravenous administration of 50jug/kg propranolol, controlled by the decrease of the pulse rate, indicates indirectly that the gastrin response to feeding is not mediated by 0-adrenergic impulses.
Gastrin Release under Propranolol in Man
367
Sham feeding had neither effect upon the mean gastrin concentration in the experiments performed with propranolol nor in the control series. This finding is in accordance with the study of Mayer et al. (6) who reported a small but not significant rise of gastrin after sham feeding in normal subjects. It seems of interest that a rise of gastrin concentration occurred in three subjects under the influence of propranolol, suggesting that a gastrin response to sham feeding is not inhibited by 0-adrenergic blockade. It has been shown in the dog that the rise of gastrin after sham feeding is suppressed by vagotomy and atropin indicat ing cholinergic intermediation (7, 11). Corresponding studies in man are not available. The persistence of the gastrin response after |3-adrenergic blockade supports indirectly the hypothesis of vagal stimulation for sham feeding in man. References
Prof. 11. Kaess. V. Medizinische Abteilung, Städtisches Krankenhaus München-Schwabing. Kölner Platz 1. D -8 München 40 (ERG)
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/6/2018 10:46:56 AM
1 Ernas, S.: Svensson. S.O.; Dörner, M., and Kaess, H.: Acid secretion and serum gastrin concentration following insulin and 2-deoxy-d-glucose in duodenal ulcer patients. Scand. J. Gastroenterol. 9: 629-637 (1974). 2 Hall, W.H.; Durkin, M.G., and Read, R.C.: Propranolol and serum gastrin in post vagotomy insulin tests. Digestion 9: 325-331 (1973). 3 Kaess, H.; Kuntzen, O.; Teckentrup, U., and Dörner, M.: The effect of propranolol on serum gastrin concentration and HCl-secretion following insulin hypoglycemia in nor mal subjects. Digestion 13: 193-200 (1975). 4 Kronborg, O.: The effect of (3-adrenergic blockade upon basal and pentagastrin stimu lated acid secretion and upon gastrin response to food. Scand. J. Gastroenterol. 10: 757-761 (1975). 5 Kronborg, O.: Pedersen, T.: Stadil, F., and Rehfeld, J.F.: The effect of (3-adrenergic blockade upon gastric acid secretion and gastrin secretion during hypoglycemia before and after vagotomy. Scand. J. Gastroenterol. 9: 173-176 (1974). 6 Mayer, G.: Arnold, R.; Feuerle, G.: Fuchs, K.:Ketlerer,H.: Track, N.S., andCreutzfeld, W.: Influence of feeding and sham feeding upon serum gastrin and gastric acid secretion in con trol subjects and duodenal ulcer patients. Scand. J. Gastroenterol. 9: 703-712 (1974). 7 Nilsson. G.: Simon, J.; Yalow, R.S., and Berson, S.A.: Plasma gastrin and gastric acid response to sham feeding and feeding in dogs. Gastroenterology 63: 51-59 (1972). 8 Shand, D.G. and Rangno, R.E.: The disposition of propranolol. 1. Elimination during oral absorption in man. Pharmacology 7: 159-168 (1972). 9 Stadil, F.: Effect of vagotomy on gastrin release during insulin hypoglycemia in ulcer patients. Scand. J. Gastroenterol. 7; 225-231 (1972). 10 Stadil, F. and Rehfeld, J.F.: Gastrin response to insulin after selective, highly selective and truncal vagotomy. Gastroenterology 66: 7 - 15 (1974). 11 Tepperman. B.L.: Walsh, J., and Preshaw, R.M.: Effect of antral denervation on gastrin release by sham feeding and insulin hypoglycemia in dogs. Gastroenterology 63: 973 980(1972). 12 Walsh. J.H. and Grossman, M.I.: Gastrin. Part I. New Engl. J. Med. 292: 1324-1334 (1975).
Serum Gastrin Concentration after Sham Feeding and Feeding under the Influence of Propranolol in Man H. Kaess, H. Fänger, U. Teckentrup and M. Dörner Department of Internal Medicine, University of Heidelberg, Heidelberg and V. Medical Department, Krankenhaus München-Schwabing, Munich
Key Words. Adrenergic (3-receptor blocker • Feeding behavior • Gastrin Abstract. The influence of propranolol, 50 Mg/kg administered intravenously, on the gastrin concentration during sham feeding and after a test meal was studied in eight normal subjects. ^-Adrenergic blockade had no inhibitory effect on the gastrin response to feeding. Sham feeding did not provoke a significant rise of serum gastrin concentration; however, in three subjects a definite gastrin response occurred in the presence of (S-adrenergic blockade.
Recently it has been shown that the gastrin release after insulin hypogly cemia in man does not result from cholinergic, but from adrenergic stimulation (3—9). (3-Adrenergic blockade with propranolol provokes a small decrease of basal gastrin concentration and abolishes the gastrin response to insulin (3). Since the hypothesis of nervous intermediation by cholinergic impulses for gastrin release after feeding was not yet established in man (12), it seemed worth while to investigate the behavior of serum gastrin in response to a test meal under the influence of (3-adrenergic blockade.
Materials and Methods The study was performed in eight male volunteers aged between 20 and 30 years. After a rest period of 30 min 50 Mg/kg propranolol (Dociton®) or 10 ml 0.9% saline in the control series, were administered intravenously. After 15 min, sham feeding was performed for a period of 30 min. Then the subjects received a test meal for a 15-ntin period. The experiments were terminated after a subsequent observation period of 120 min. The order of the test was randomized. During the experiment venous blood samples were collected through a catheter, placed in a antecubital vein. Pulse rate and arterial blood pressure were noted. Serum specimens
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/6/2018 10:46:56 AM
Received: January 5, 1976; accepted: March 16, 1976.
Kaess/Fànger/Teckentmp/Dorner
365
were stored at 20 °C until gastrin was determined (3). All samples of a single subject were tested in the same assay. The intra-assay variance was 10% and the interassay 15%. The meal included 150g sirloin steak, boiled potatoes with butter (25 g) and mineral water (200 ml). For sham feeding the subjects were only allowed to see and to smell the freshly prepared test meal. The results are presented as means and standard errors of the mean. Student test for unpaired values was used for calculation of p values. The integrated response of gastrin was calculated as described previously (1. 3). The gastrin concentrations after starting the test meal were compared with mean basal gastrin concentration.
Results In the control series the serum gastrin concentration remained unchanged during sham feeding (fig. 1). After the meal the gastrin concentration in creased significantly from 75 to 99 pg/ml at 45 min (p < 0.01) and decreased slowly to 89 pg/ml at the end of the experiment. In the test series serum gastrin decreased from 75 to 70 pg/ml (p < 0.05) after administration of propranolol. During sham feeding the rise of gastrin from 70 to 80 pg/ml was not significant. Feeding resulted in a sustained gastrin response which did not differ significantly from the gastrin rise in the control experiments. The analysis of the results during sham feeding shows a rise of gastrin concentration above the mean basal concentration in one subject of the control series (15 %) and in three subjects in the propranolol series (28. 30 and 48 %).
Fig. 1. Serum gastrin concentration after sham feeding and feeding under the effect of propranolol (50 jug/kg) intravenously.
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/6/2018 10:46:56 AM
m in
Kaess /Fänger/Teckentrup/Dörner
366
6
5 A
Control
Propranolol
Fig. 2. Integrated gastrin response to feeding (ng/2 hi.
The integrated gastrin output after the test meal was 1.9 ng/2 h and 2.9 ng/2 h in the experiments performed under the influence of propranolol (fig. 2). The pulse rate was significantly lower after propranolol than in the control experiments.
Discussion
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/6/2018 10:46:56 AM
The present study indicates that the rise of serum gastrin following a test meal is not inhibited by propranolol. This result is in contrast to the behavior of gastrin after insulin hypoglycemia under the influence of (3-adrenergic blockade with this substance (3). Under these conditions a small decrease of basal gastrin and suppression of the gastrin response occurred, associated with a decrease of the HC1 secretion. Contradictory findings of previous authors, who had reported an unchanged gastrin response to insulin after 20 mg propranolol given orally, must be related to the different dosage and the route of administration of the drug (2, 5). A single oral dose of propranolol below 30 mg is completely extracted from the liver by high tissue affinity binding (8). Therefore, the unchanged gastrin re sponse to feeding after 40 mg propranolol orally, reported recently by Kronborg (4) is not enequivocal. In the present study the rise of gastrin, which occurs under (3-adrenergic blockade, with intravenous administration of 50jug/kg propranolol, controlled by the decrease of the pulse rate, indicates indirectly that the gastrin response to feeding is not mediated by 0-adrenergic impulses.
Gastrin Release under Propranolol in Man
367
Sham feeding had neither effect upon the mean gastrin concentration in the experiments performed with propranolol nor in the control series. This finding is in accordance with the study of Mayer et al. (6) who reported a small but not significant rise of gastrin after sham feeding in normal subjects. It seems of interest that a rise of gastrin concentration occurred in three subjects under the influence of propranolol, suggesting that a gastrin response to sham feeding is not inhibited by 0-adrenergic blockade. It has been shown in the dog that the rise of gastrin after sham feeding is suppressed by vagotomy and atropin indicat ing cholinergic intermediation (7, 11). Corresponding studies in man are not available. The persistence of the gastrin response after |3-adrenergic blockade supports indirectly the hypothesis of vagal stimulation for sham feeding in man. References
Prof. 11. Kaess. V. Medizinische Abteilung, Städtisches Krankenhaus München-Schwabing. Kölner Platz 1. D -8 München 40 (ERG)
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/6/2018 10:46:56 AM
1 Ernas, S.: Svensson. S.O.; Dörner, M., and Kaess, H.: Acid secretion and serum gastrin concentration following insulin and 2-deoxy-d-glucose in duodenal ulcer patients. Scand. J. Gastroenterol. 9: 629-637 (1974). 2 Hall, W.H.; Durkin, M.G., and Read, R.C.: Propranolol and serum gastrin in post vagotomy insulin tests. Digestion 9: 325-331 (1973). 3 Kaess, H.; Kuntzen, O.; Teckentrup, U., and Dörner, M.: The effect of propranolol on serum gastrin concentration and HCl-secretion following insulin hypoglycemia in nor mal subjects. Digestion 13: 193-200 (1975). 4 Kronborg, O.: The effect of (3-adrenergic blockade upon basal and pentagastrin stimu lated acid secretion and upon gastrin response to food. Scand. J. Gastroenterol. 10: 757-761 (1975). 5 Kronborg, O.: Pedersen, T.: Stadil, F., and Rehfeld, J.F.: The effect of (3-adrenergic blockade upon gastric acid secretion and gastrin secretion during hypoglycemia before and after vagotomy. Scand. J. Gastroenterol. 9: 173-176 (1974). 6 Mayer, G.: Arnold, R.; Feuerle, G.: Fuchs, K.:Ketlerer,H.: Track, N.S., andCreutzfeld, W.: Influence of feeding and sham feeding upon serum gastrin and gastric acid secretion in con trol subjects and duodenal ulcer patients. Scand. J. Gastroenterol. 9: 703-712 (1974). 7 Nilsson. G.: Simon, J.; Yalow, R.S., and Berson, S.A.: Plasma gastrin and gastric acid response to sham feeding and feeding in dogs. Gastroenterology 63: 51-59 (1972). 8 Shand, D.G. and Rangno, R.E.: The disposition of propranolol. 1. Elimination during oral absorption in man. Pharmacology 7: 159-168 (1972). 9 Stadil, F.: Effect of vagotomy on gastrin release during insulin hypoglycemia in ulcer patients. Scand. J. Gastroenterol. 7; 225-231 (1972). 10 Stadil, F. and Rehfeld, J.F.: Gastrin response to insulin after selective, highly selective and truncal vagotomy. Gastroenterology 66: 7 - 15 (1974). 11 Tepperman. B.L.: Walsh, J., and Preshaw, R.M.: Effect of antral denervation on gastrin release by sham feeding and insulin hypoglycemia in dogs. Gastroenterology 63: 973 980(1972). 12 Walsh. J.H. and Grossman, M.I.: Gastrin. Part I. New Engl. J. Med. 292: 1324-1334 (1975).
