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The pharmacology of post prandial somatostatin release in man
S12 matostatin secretion in man. 2) Inhibition of gastric acid with cimetidin~ reduces somatostatin secretion during an insulin-induced hypoglycaemia, and 3) Gastric acid mediates somatostatin secretion associated with insulin -induced hypoglycaemia in man.
HISTAMINE INFUSION INCREASES SOMATOSTATIN LIKE IMMUNOREACTIVITY IN GASTRIC JUICE AND PERIPHERAL VENOUS BLOOD IN MAN S. Skare, L.E. Hanssen and K.F. Hanssen - Hormone Laboratory and Med. Dept. B, Aker Hospital, and Research Dept. of Gastroenterology, UllevAl Hospital, Oslo, Norway Somatostatin is produced in the D-cells of the gastric mucosa, and somatostatin is present in the gastric j u i c e . We have shown that pentagastrin infusion leads to a rapid somatostatin elevation in peripheral venous plasma and gastric j u i c e in 8 healthy, young persons (Third International Symposium on Gastrointestinal Hormones, Cambridge, 1980). The aim of the present study was to test whether this could be reproduced by other gastric acid stimulators. Eight healthy, young persons received fasting an iv infusion of histamine, 25.6 ~g/kg/h, for 80 min from 8 a.m. Another 8 healthy, young persons received in addition to histamine 25.6 ~g/kg/h, TRH 500 ~g/h, known to i n h i b i t gastric juice production, for the last 40 min of the histamine infusion period. Blood samples were drawn frequently from the opposite arm into c h i l l e d lithium heparin tubes and kept at 4oc until the plasma was frozen. Gastric j u i c e was collected every lOth min, 2 ml was immediately extracted. Gastric juice and plasma were assayed for somatostatin a f t e r extraction with 95% aceton, 2:1, using a rabbit antibody reacting with the central portion of the molecule. Gastric juice SLI concentration increased from mean basal value 174.6 ± 26.7 pmol/l to mean 439.2 ± 63.0 pmol/l (p<0.05) during histamine stimulation, being even higher, 739.6 ± 65.0 pmol/l, in the 40 min post infusion period (p
THE PHARMACOLOGYOF POST PRANDIAL SOMATOSTATIN RELEASE IN MAN. J.A.H. Wass, Erica Penman*, Susam Webb, M. Lucey +, I. Barrow, Lesley H. Rees* and G.M. Besser. Departments of Endocrinology, Chemical Endocrinology* and Gastroenterology + , St. Bartholomew's Hospital, London, ECIA 7BE, U.K. Plasma somatostatin rises in man a f t e r food, and there is evidence that this increase derives largely from the gastrointestinal t r a c t and pancreas. We have already demonstrated that blockade of H2 receptors with cimetidine sign i f i c a n t l y decreases the somatostatin responses to a standard meal. In this series of experiments, we have assessed the e f f e c t of blockade of cholinergic, ~ and 8 receptors with atropine (0.04 mg/kg i . m . ) , thymoxamine (0.1 mg/kg i . v . over 2 minutes, then 10 mg/kg/hour over 2 hours) and propranolol 0.15 mg/kg i . v . over 2 minutes, then 0.075 mg/kg/hour over 2 hours). D i f f e r ent groups of six normal subjects were each given on separate occasions, double blind, a standard meal (67 g carbohydrate, 20 g fat and 17 g protein)
S13
over 15 minutes with either saline or the active drug. Atropine was given intramuscularly; thymoxamine and propranolol were given intravenously with a bolus dose followed by a two hour continuous intravenous infusion. Blood samples were taken and somatostatin measured by a specific and sensitive radioimmunoassay1. There was an immediate and sustained rise in plasma somatostatin following the standard meal in all the normal subjects during saline (mean basal : I SE, 11.1 ± 1.05 pg/ml rising to a peak at 60 minutes of 27.2 ± 3.4 pg/ml). Atropine abolished this rise induced by food (mean basal 10.6 ~ 1.0 pg/ml rising to a peak at 30 minutes of 16.3 ± 3.2 pg/ml. In contrast, no significant decrease in somatostatin release induced by food was observed during the thymoxamine and propranolol infusions. It is concluded that cholinergic mechanisms are important in the post prandial release of somatostatin in man. I. Penman, E. et al.
GASTRIN
RELEASE
Annals of Clinical Biochemistry, 16, 15-25, 1979.
IN M O D I F I E D
SHAM FEEDING
O. Wis~n, R. Befrits, C. Johansson, K. Samuelsson & K. Uvn~s-Moberg. Medicine, Karolinska Hospital, S-I04 01 Stockholm, Sweden.
Dept of
Most authors have failed to demonstate significant gastrin release in response to sham feeding in man. In this study we have determined plasma gastrin levels and intraluminal gastrin release in response to m o d i f i e d sham feeding (MSF). Methods: i0 h e a l t h y volunteers, 21-59 years old, were sham fed for 15 min. Gastric contents were collected for 4 x 15 min before and for 8 x 15 min during and after MSF. The stomach was p e r f u s e d with isotonic mannitol solution i0 ml/min with vit. BI2 as a marker. 50 ml of each sample was reduced to I/5 by b o i l i n g and then kept frozen until analysed for gastrin. Venous blood was obtained by an indwelling catheter. Gastrin was analysed by r a d i o i m m u n o a s s a y using Rehfeld a n t i s e r u m 2604. Results: MSF 60'-75'
45'
Gastrin/plasma ng/1 M±SE
60'
75'
90'
34.7 ±5.8
34.7 +7.2
36.6 +6.4
105'
120'
135'
32.5 ±5.9
150' 30.3 ±5.5
Gastrin/perfusates ng/15' MiSE
1.27 ±0.12
1.22 ±0.18
2.26 ±0.61
2.45 ±0.41
2.29 +0.58
1.44 ±0.19
1.59 ±0.24
1.51 ±0.24
HC1/perfusates mmol/15' M±SE
0.60 ±0.12
0.66 ±0.18
2.02 ±0.45
2.71 ±0.55
1.89 ±0.44
1.37 ±0.27
1.30 ±0.26
0.91 ±0.19
EA EA ~A
gastrin/plasma gastrin/perf. HCl/perf.
60' - 150' 60' - 150' 60' - 150'
- 85.5 ± 226.1 ng-min.l -I 3.98 i 0.99 ng (p<0.0025) 6.42 ± 1.62 mmol (p<0.0025)
Gastrin levels in perfusates were significantly increased in response to MSF, whereas plasma gastrin levels were u n c h a n g e d throughout the experiments. A high correlation between integrated HC1 and perfusate gastrin responses were recorded (r=0.83; n=10). Conclusions: The results indicate that gastrin is released in response t o M S F , the changes being more clearly recorded intraluminally than in plasma.
Secretin is an enterogastrone in humans. Chul H. You, William Y. Chey. Issac Gordon Center for Digestive Diseases and Nutrition, The Genesee Hospital and Univ. of Rochester School of Medicine and Dentistry, Rochester,N.Y. 14607, USA. Secretin in a physiological dose, 0.03 or 0.06 clinical unit(CU) was shown to significantly inhibit gastric acid secretion stimulated by iv synthetic human
HISTAMINE INFUSION INCREASES SOMATOSTATIN LIKE IMMUNOREACTIVITY IN GASTRIC JUICE AND PERIPHERAL VENOUS BLOOD IN MAN S. Skare, L.E. Hanssen and K.F. Hanssen - Hormone Laboratory and Med. Dept. B, Aker Hospital, and Research Dept. of Gastroenterology, UllevAl Hospital, Oslo, Norway Somatostatin is produced in the D-cells of the gastric mucosa, and somatostatin is present in the gastric j u i c e . We have shown that pentagastrin infusion leads to a rapid somatostatin elevation in peripheral venous plasma and gastric j u i c e in 8 healthy, young persons (Third International Symposium on Gastrointestinal Hormones, Cambridge, 1980). The aim of the present study was to test whether this could be reproduced by other gastric acid stimulators. Eight healthy, young persons received fasting an iv infusion of histamine, 25.6 ~g/kg/h, for 80 min from 8 a.m. Another 8 healthy, young persons received in addition to histamine 25.6 ~g/kg/h, TRH 500 ~g/h, known to i n h i b i t gastric juice production, for the last 40 min of the histamine infusion period. Blood samples were drawn frequently from the opposite arm into c h i l l e d lithium heparin tubes and kept at 4oc until the plasma was frozen. Gastric j u i c e was collected every lOth min, 2 ml was immediately extracted. Gastric juice and plasma were assayed for somatostatin a f t e r extraction with 95% aceton, 2:1, using a rabbit antibody reacting with the central portion of the molecule. Gastric juice SLI concentration increased from mean basal value 174.6 ± 26.7 pmol/l to mean 439.2 ± 63.0 pmol/l (p<0.05) during histamine stimulation, being even higher, 739.6 ± 65.0 pmol/l, in the 40 min post infusion period (p
THE PHARMACOLOGYOF POST PRANDIAL SOMATOSTATIN RELEASE IN MAN. J.A.H. Wass, Erica Penman*, Susam Webb, M. Lucey +, I. Barrow, Lesley H. Rees* and G.M. Besser. Departments of Endocrinology, Chemical Endocrinology* and Gastroenterology + , St. Bartholomew's Hospital, London, ECIA 7BE, U.K. Plasma somatostatin rises in man a f t e r food, and there is evidence that this increase derives largely from the gastrointestinal t r a c t and pancreas. We have already demonstrated that blockade of H2 receptors with cimetidine sign i f i c a n t l y decreases the somatostatin responses to a standard meal. In this series of experiments, we have assessed the e f f e c t of blockade of cholinergic, ~ and 8 receptors with atropine (0.04 mg/kg i . m . ) , thymoxamine (0.1 mg/kg i . v . over 2 minutes, then 10 mg/kg/hour over 2 hours) and propranolol 0.15 mg/kg i . v . over 2 minutes, then 0.075 mg/kg/hour over 2 hours). D i f f e r ent groups of six normal subjects were each given on separate occasions, double blind, a standard meal (67 g carbohydrate, 20 g fat and 17 g protein)
S13
over 15 minutes with either saline or the active drug. Atropine was given intramuscularly; thymoxamine and propranolol were given intravenously with a bolus dose followed by a two hour continuous intravenous infusion. Blood samples were taken and somatostatin measured by a specific and sensitive radioimmunoassay1. There was an immediate and sustained rise in plasma somatostatin following the standard meal in all the normal subjects during saline (mean basal : I SE, 11.1 ± 1.05 pg/ml rising to a peak at 60 minutes of 27.2 ± 3.4 pg/ml). Atropine abolished this rise induced by food (mean basal 10.6 ~ 1.0 pg/ml rising to a peak at 30 minutes of 16.3 ± 3.2 pg/ml. In contrast, no significant decrease in somatostatin release induced by food was observed during the thymoxamine and propranolol infusions. It is concluded that cholinergic mechanisms are important in the post prandial release of somatostatin in man. I. Penman, E. et al.
GASTRIN
RELEASE
Annals of Clinical Biochemistry, 16, 15-25, 1979.
IN M O D I F I E D
SHAM FEEDING
O. Wis~n, R. Befrits, C. Johansson, K. Samuelsson & K. Uvn~s-Moberg. Medicine, Karolinska Hospital, S-I04 01 Stockholm, Sweden.
Dept of
Most authors have failed to demonstate significant gastrin release in response to sham feeding in man. In this study we have determined plasma gastrin levels and intraluminal gastrin release in response to m o d i f i e d sham feeding (MSF). Methods: i0 h e a l t h y volunteers, 21-59 years old, were sham fed for 15 min. Gastric contents were collected for 4 x 15 min before and for 8 x 15 min during and after MSF. The stomach was p e r f u s e d with isotonic mannitol solution i0 ml/min with vit. BI2 as a marker. 50 ml of each sample was reduced to I/5 by b o i l i n g and then kept frozen until analysed for gastrin. Venous blood was obtained by an indwelling catheter. Gastrin was analysed by r a d i o i m m u n o a s s a y using Rehfeld a n t i s e r u m 2604. Results: MSF 60'-75'
45'
Gastrin/plasma ng/1 M±SE
60'
75'
90'
34.7 ±5.8
34.7 +7.2
36.6 +6.4
105'
120'
135'
32.5 ±5.9
150' 30.3 ±5.5
Gastrin/perfusates ng/15' MiSE
1.27 ±0.12
1.22 ±0.18
2.26 ±0.61
2.45 ±0.41
2.29 +0.58
1.44 ±0.19
1.59 ±0.24
1.51 ±0.24
HC1/perfusates mmol/15' M±SE
0.60 ±0.12
0.66 ±0.18
2.02 ±0.45
2.71 ±0.55
1.89 ±0.44
1.37 ±0.27
1.30 ±0.26
0.91 ±0.19
EA EA ~A
gastrin/plasma gastrin/perf. HCl/perf.
60' - 150' 60' - 150' 60' - 150'
- 85.5 ± 226.1 ng-min.l -I 3.98 i 0.99 ng (p<0.0025) 6.42 ± 1.62 mmol (p<0.0025)
Gastrin levels in perfusates were significantly increased in response to MSF, whereas plasma gastrin levels were u n c h a n g e d throughout the experiments. A high correlation between integrated HC1 and perfusate gastrin responses were recorded (r=0.83; n=10). Conclusions: The results indicate that gastrin is released in response t o M S F , the changes being more clearly recorded intraluminally than in plasma.
Secretin is an enterogastrone in humans. Chul H. You, William Y. Chey. Issac Gordon Center for Digestive Diseases and Nutrition, The Genesee Hospital and Univ. of Rochester School of Medicine and Dentistry, Rochester,N.Y. 14607, USA. Secretin in a physiological dose, 0.03 or 0.06 clinical unit(CU) was shown to significantly inhibit gastric acid secretion stimulated by iv synthetic human