GastroenterologiaJaponica Copyright 9 by TheJapanese Society of Gastroenterology
Vol. 13, No. 3 Printed inJapan
- - O r i g i n a l Article--
EFFECT OF I N T R A V E N O U S I N F U S I O N OF S O M A T O S T A T I N ON GASTRIC, PANCREATIC AND BILIARY SECRETION IN THE RAT Motoyuki M O R I G A , M.D.1), Koichi K O J I M A , M.D.1), Mitsuru A O N O , M.D.a), H a r u t o U C H I N O , M.D. 1) a n d H a r u a k i YAJIMA, M.D. s)
The First Division of Internal Medicine, Faculty of Medicinet), and Faculty of Pharmaceutical Sciences2), Kyoto University, Sakyo-ku, Kyoto, 606Japan
Summary The effect of somatostatin (GH-RIH) on gastric, pancreatic and biliary secretion was examined in the anesthetized rats. Intraveous infusion of the hormone, in graded doses ranging from 1 to 16/~g/kg/hr, produced a dosedependent inhibition of pentagastrin, 1.5/zg/kg/hr, induced acid secretion, reaching about 54% of control level at the dose of 16/tg/kg/hr. Somatostatin, 4, 16 and 64gg/kg/hr, inhibited the pancreatic juice volume stimulated by intravenous injection of secretin, 1 u/kg, as a bolus. Somatostatin, 2, 8, 32 and 128/zg/kg/30 rain, did not change the bile flow rate in control period. Somatostatin may play a physiological role in the regulation of the secretory process of the stomach and pancreas. Key Words:
somatostatin, Ghosh-Lai's rat, Love's rat, gastric and pancreatic secretion.
Introduction Somatostatin, a g r o w t h - h o r m o n e release inh i b i t i n g h o r m o n e , isolated originally from ovine h y p o t h a l a m u s by Brazeau et al. 1) was f o u n d in the rat s t o m a c h a n d pancreas in high concentrations, similar to that in the brainS). T h e intravenous infusion of this h o r m o n e inhibits the release of g r o w t h h o r m o n O , s), TSH4), insulinS,6), glucagon6,7), gastrinS,9), secretin 10) a n d CCK-PZXl). These informations suggest that somatostatin m a y play a physiological role in the reg u l a t i o n of the secretory process of the s t o m a c h a n d pancreas. Received March 3, 1978. Accepted March 13, 1978. Address requests for reprints to: Dr. Motoyuki Moriga, M.D., 1st Department of Internal Medicine, Faculty of Medicine, Kyoto University, Kawaramachi, Shogoin, Sakyo-Ku, Kyoto, 606Japan.
T h e present study was p e r f o r m e d to investigate the effect of somatostatin on gastrointestinal secretions in the anesthetized rats. Materials and Methods Female Wistar albino rats weighing 2 0 0 - 2 5 0 g were used in the experiments. T h e animals were not starved, a n d were anesthetized by a single i n t r a m u s c u l a r injection of uret h a n e (0.7 m l / 1 0 0 g b o d y weight of a 25 % solution). Body t e m p e r a t u r e of the rat was m a i n t a i n e d at 36+-1~ by m e a n s of a rectal p r o b e a n d a w a r m i n g system t h r o u g h o u t the study. Bilateral femoral veins were c a n n u l a t e d for injections a n d infusions. T h e effect of s o m a t o s t a t i n on gastric secretion was tested in the Ghosh-Lai rat p r e p a r a tiont2,xs). T h e r a t s t o m a c h p r e p a r a t i o n was perfused with a p h o s p h a t e - c i t r a t e buffer in saline
J u n e 1978
191
Somatostatin on R a t Gastrointestinal Secretion
of p H 6.6 at 36~ using an automatic peristaltic p u m p that delivered the buffer at a rate of l m l / m i n . The 15-min aliquots of perfusate were collected continuously, and used for the determination of acid and pepsin contents. Acid output was determined by titration to pH 7.0 with 0.01N N a O H using a automatic titrator assembly. Pepsin activity was measured by the method of Anson-MirskyX4). The results were calculated as the output during every 30 rain period. The results were also expressed as the percentage of the outputs of acid and pepsin occurring in the period immediately before somatostatin infusion. Gastric secretion was stimulated by an intravenous infusion of pentagastrin (ICI, England), 1.5, 3 and 6/.tg/kg/hr. Somatostatin (Synthetic cyclic peptida; Yajima H, Chem Pharm Bull 23: 1956, 1975) was infused for one hour in graded doses of 1, 4, 8 and 16/.tg/kg/hr. The effect of somatostatin on pancreatic secretion was tested in the Love-Tachibana rat preparationl~.a6). In tests measuring the maximal pancreatic flow of the preparation with secretory stimulant, secretin was injected using an incremental 30 rain step-dose method. Pancreatic secretion was stimulated by an intravenous injection of secretin (Eisai, Japan), 1 u/kg, to about 80% of the m a x i m u m output. Secretin was given as a bolus injection at the beginning of each 30 min period. In some cases, two secretin dosages, 0.25 and 0.5 u / k g as a bolus, were used as the stimulant. Pancreatic juice was collected every 30 min and the volume was measured. The effect of addition of somatostatin on these pancreatic responses was studied. Somatostatin was added in graded doses of 4, 16 and 64/tg/kg/hr. The effect of somatostatin on the secretion of bile was studied by the Love-Tachibana's methodlSa6). The bile flow, through a complete outer drainage, was measured for one 15 min basal and eight 15-min secretions during
somatostatin infusion. Somatostatin was infused in graded doses of 2, 8, 32 and 128/.tg/kg/30 min. All the experiments were statistically evaluated with Student's t test for non-paired values, p
Vol. 13, No. 3 Printed inJapan
- - O r i g i n a l Article--
EFFECT OF I N T R A V E N O U S I N F U S I O N OF S O M A T O S T A T I N ON GASTRIC, PANCREATIC AND BILIARY SECRETION IN THE RAT Motoyuki M O R I G A , M.D.1), Koichi K O J I M A , M.D.1), Mitsuru A O N O , M.D.a), H a r u t o U C H I N O , M.D. 1) a n d H a r u a k i YAJIMA, M.D. s)
The First Division of Internal Medicine, Faculty of Medicinet), and Faculty of Pharmaceutical Sciences2), Kyoto University, Sakyo-ku, Kyoto, 606Japan
Summary The effect of somatostatin (GH-RIH) on gastric, pancreatic and biliary secretion was examined in the anesthetized rats. Intraveous infusion of the hormone, in graded doses ranging from 1 to 16/~g/kg/hr, produced a dosedependent inhibition of pentagastrin, 1.5/zg/kg/hr, induced acid secretion, reaching about 54% of control level at the dose of 16/tg/kg/hr. Somatostatin, 4, 16 and 64gg/kg/hr, inhibited the pancreatic juice volume stimulated by intravenous injection of secretin, 1 u/kg, as a bolus. Somatostatin, 2, 8, 32 and 128/zg/kg/30 rain, did not change the bile flow rate in control period. Somatostatin may play a physiological role in the regulation of the secretory process of the stomach and pancreas. Key Words:
somatostatin, Ghosh-Lai's rat, Love's rat, gastric and pancreatic secretion.
Introduction Somatostatin, a g r o w t h - h o r m o n e release inh i b i t i n g h o r m o n e , isolated originally from ovine h y p o t h a l a m u s by Brazeau et al. 1) was f o u n d in the rat s t o m a c h a n d pancreas in high concentrations, similar to that in the brainS). T h e intravenous infusion of this h o r m o n e inhibits the release of g r o w t h h o r m o n O , s), TSH4), insulinS,6), glucagon6,7), gastrinS,9), secretin 10) a n d CCK-PZXl). These informations suggest that somatostatin m a y play a physiological role in the reg u l a t i o n of the secretory process of the s t o m a c h a n d pancreas. Received March 3, 1978. Accepted March 13, 1978. Address requests for reprints to: Dr. Motoyuki Moriga, M.D., 1st Department of Internal Medicine, Faculty of Medicine, Kyoto University, Kawaramachi, Shogoin, Sakyo-Ku, Kyoto, 606Japan.
T h e present study was p e r f o r m e d to investigate the effect of somatostatin on gastrointestinal secretions in the anesthetized rats. Materials and Methods Female Wistar albino rats weighing 2 0 0 - 2 5 0 g were used in the experiments. T h e animals were not starved, a n d were anesthetized by a single i n t r a m u s c u l a r injection of uret h a n e (0.7 m l / 1 0 0 g b o d y weight of a 25 % solution). Body t e m p e r a t u r e of the rat was m a i n t a i n e d at 36+-1~ by m e a n s of a rectal p r o b e a n d a w a r m i n g system t h r o u g h o u t the study. Bilateral femoral veins were c a n n u l a t e d for injections a n d infusions. T h e effect of s o m a t o s t a t i n on gastric secretion was tested in the Ghosh-Lai rat p r e p a r a tiont2,xs). T h e r a t s t o m a c h p r e p a r a t i o n was perfused with a p h o s p h a t e - c i t r a t e buffer in saline
J u n e 1978
191
Somatostatin on R a t Gastrointestinal Secretion
of p H 6.6 at 36~ using an automatic peristaltic p u m p that delivered the buffer at a rate of l m l / m i n . The 15-min aliquots of perfusate were collected continuously, and used for the determination of acid and pepsin contents. Acid output was determined by titration to pH 7.0 with 0.01N N a O H using a automatic titrator assembly. Pepsin activity was measured by the method of Anson-MirskyX4). The results were calculated as the output during every 30 rain period. The results were also expressed as the percentage of the outputs of acid and pepsin occurring in the period immediately before somatostatin infusion. Gastric secretion was stimulated by an intravenous infusion of pentagastrin (ICI, England), 1.5, 3 and 6/.tg/kg/hr. Somatostatin (Synthetic cyclic peptida; Yajima H, Chem Pharm Bull 23: 1956, 1975) was infused for one hour in graded doses of 1, 4, 8 and 16/.tg/kg/hr. The effect of somatostatin on pancreatic secretion was tested in the Love-Tachibana rat preparationl~.a6). In tests measuring the maximal pancreatic flow of the preparation with secretory stimulant, secretin was injected using an incremental 30 rain step-dose method. Pancreatic secretion was stimulated by an intravenous injection of secretin (Eisai, Japan), 1 u/kg, to about 80% of the m a x i m u m output. Secretin was given as a bolus injection at the beginning of each 30 min period. In some cases, two secretin dosages, 0.25 and 0.5 u / k g as a bolus, were used as the stimulant. Pancreatic juice was collected every 30 min and the volume was measured. The effect of addition of somatostatin on these pancreatic responses was studied. Somatostatin was added in graded doses of 4, 16 and 64/tg/kg/hr. The effect of somatostatin on the secretion of bile was studied by the Love-Tachibana's methodlSa6). The bile flow, through a complete outer drainage, was measured for one 15 min basal and eight 15-min secretions during
somatostatin infusion. Somatostatin was infused in graded doses of 2, 8, 32 and 128/.tg/kg/30 min. All the experiments were statistically evaluated with Student's t test for non-paired values, p
