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Gastric somatostatin as a mediator of the enterogastrone action of gastric inhibitory polypeptide (GIP)
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GASTRIC SOMATOSTATIN AS A MEDIATOR OF THE ENTEROGASTRONE INHIBITORY POLYPEPTIDE (GIP)
ACTION OF GASTRIC
C H S Mclntosh, R A Pederson and J C Brown, University of British Columbia, Vancouver, CANADA. GIP is only a weak enterogastrone in the innervated stomach and its potent acid inhibitory action in the denervated stomach is reversed by cholinomimetics. Gastric somatostatin-like immunoreactivity (SLI) is a potential local acid inhibitor. The effect of GIP on SLI secretion from an isolated perfused rat stomach and the interaction of acetylcholine (ACh) and vagal stimulation have been studied. The stomach of fasted rats was isolated with vasculature intact by division of the pylorus. Pancreas, spleen, small bowel and colon were removed. Perfusate (Krebs bicarbonate buffer, 0.2% HSA, 3% dextran pH 7.4) was introduced into the celiac artery (3 ml/min). Portal vein effluent was collected in i000 KIU/ml Trasylol. SLI was measured by specific radioimmunoassay. GIP (5 ng/ml) increased SLI secretion from a basal 766 ~ 152 pg/min to 3737 ~ 999 pg/min after 5 min. At a higher dose of GIP (50 ng/ml) SLI secretion increased from 1219 ~ 168 pg/min to 15077 ~ 3545 pg/min after 2 min and subsequently declined throughout the perfusion. Integrated output accounted for most of the gastric store measured in tissue extracts. Capacity to synthesize was thus exceeded by high GIP stimulation. ACh (i0 ~M) or vagal stimulation completely inhibited GIP (5 ng/ml) stimulated SLI secretion. Basal SLI output was also inhibited by ACh. The potent somatostatinotropic capacity of GIP suggests that endogenous SLI is the mediator of its enterograstrone activity. Cholinergic inhibition explains the weak activity in the innervated stomach.
TIiE ACTION OF SAUVAGINE GN TIqE M E S E N T E R I C VASCULAR GED AND I N T E S T I N A L A B S O R P T I O N IN A N A E S T H E T I Z E D DOGS P . M e l c h i o r r i and L. N e g r i , I n s t i t u t e of P h a r m a c o l o g y , U n i v . o f Rome, I t a l y A m i n o a c i d s e q u e n c e of S a u v a g i n e (SV) , a peptide i s o l a t e d from the skin of the f r o g P h y l l o m e d u s a s a u v a g e i g h a s b e e n d e m o n s t r a t e d to be: Pyr-Gly-Pro-Pro-Ile - Ser-Ile-Asp- Leu- Set- Leu-Glu-Leu-Leu-Arg-Lys-Met Ile - G l u - I l e - G l u - L y s - G l n - G l u - L y s - G l u - L y s - G l n - G l n - A l a - A l a - A s n - A s n - A r g L e u - L e u - L e u - A s p - T h r - I l e - N H 2 . ( m . wt. 3780) M e s e n t e r i e blood flow and i t s d i s t r i b u t i o n b e t w e e n m u c o s a l p l u s s u b m u c o s a l and m u s c o l a r l a y e r s of dog i n t e s t i n e w e r e m e a s u r e d by e l e c t r o m a g n e t i c flowm e t e r and r a d i o a c t i v e m i c r o s p h e r e t e c n i q u e ~ r e s p e c t i v e l y . I n t e s t i n a l a b s o r p t i on of w a t e r , N a , K , C 1 , H C O 3 , w a s m e a s u r e d , i n v i v o , i n c l o s e d i l e a l loops of 12 dogs . I n t r a v e n o u s i n f u s i o n of SV (3, 5, 1 0 , 2 0 , 3 0 n g / k g / m i n ) p r o d u c e d a dose r e l a t e d i n c r e a s e of m e s e n t e r i c blood flow up to 3OOG c o n t r o l v a f u e s . M u c o s a l blood flow od ileum and colon was i n c r e a s e d , w h i l e m u s c o l a r blood flow w a s unaffected or slightly decreased.lntestinal absorption of w a t e r a n d e l e ctrolytes w a s r e v e r s e d to secretion~due to a significant d e c r e a s e in absorpti ve fluxes a n d increase in s e c r e t o r y fluxes.lt w a s c o n c l u d e d thaf S V di s p l a y s m a r k e d selectivity in p r o d u c i n g m e s e n t e r i c vasodilatation in the a p p a r e n t abs e n c e of other significant c a r d i o v a s c u l a r effects.The increase in m e s e n [ e r i c blood flow a p p e a r s to be restricted to s e c r e t o r y sites of intestinal m u c o s a a n d related to s e c r e t o r y fluxes of b i c a r b o n a t e s a n d w a ter.
GASTRIC SOMATOSTATIN AS A MEDIATOR OF THE ENTEROGASTRONE INHIBITORY POLYPEPTIDE (GIP)
ACTION OF GASTRIC
C H S Mclntosh, R A Pederson and J C Brown, University of British Columbia, Vancouver, CANADA. GIP is only a weak enterogastrone in the innervated stomach and its potent acid inhibitory action in the denervated stomach is reversed by cholinomimetics. Gastric somatostatin-like immunoreactivity (SLI) is a potential local acid inhibitor. The effect of GIP on SLI secretion from an isolated perfused rat stomach and the interaction of acetylcholine (ACh) and vagal stimulation have been studied. The stomach of fasted rats was isolated with vasculature intact by division of the pylorus. Pancreas, spleen, small bowel and colon were removed. Perfusate (Krebs bicarbonate buffer, 0.2% HSA, 3% dextran pH 7.4) was introduced into the celiac artery (3 ml/min). Portal vein effluent was collected in i000 KIU/ml Trasylol. SLI was measured by specific radioimmunoassay. GIP (5 ng/ml) increased SLI secretion from a basal 766 ~ 152 pg/min to 3737 ~ 999 pg/min after 5 min. At a higher dose of GIP (50 ng/ml) SLI secretion increased from 1219 ~ 168 pg/min to 15077 ~ 3545 pg/min after 2 min and subsequently declined throughout the perfusion. Integrated output accounted for most of the gastric store measured in tissue extracts. Capacity to synthesize was thus exceeded by high GIP stimulation. ACh (i0 ~M) or vagal stimulation completely inhibited GIP (5 ng/ml) stimulated SLI secretion. Basal SLI output was also inhibited by ACh. The potent somatostatinotropic capacity of GIP suggests that endogenous SLI is the mediator of its enterograstrone activity. Cholinergic inhibition explains the weak activity in the innervated stomach.
TIiE ACTION OF SAUVAGINE GN TIqE M E S E N T E R I C VASCULAR GED AND I N T E S T I N A L A B S O R P T I O N IN A N A E S T H E T I Z E D DOGS P . M e l c h i o r r i and L. N e g r i , I n s t i t u t e of P h a r m a c o l o g y , U n i v . o f Rome, I t a l y A m i n o a c i d s e q u e n c e of S a u v a g i n e (SV) , a peptide i s o l a t e d from the skin of the f r o g P h y l l o m e d u s a s a u v a g e i g h a s b e e n d e m o n s t r a t e d to be: Pyr-Gly-Pro-Pro-Ile - Ser-Ile-Asp- Leu- Set- Leu-Glu-Leu-Leu-Arg-Lys-Met Ile - G l u - I l e - G l u - L y s - G l n - G l u - L y s - G l u - L y s - G l n - G l n - A l a - A l a - A s n - A s n - A r g L e u - L e u - L e u - A s p - T h r - I l e - N H 2 . ( m . wt. 3780) M e s e n t e r i e blood flow and i t s d i s t r i b u t i o n b e t w e e n m u c o s a l p l u s s u b m u c o s a l and m u s c o l a r l a y e r s of dog i n t e s t i n e w e r e m e a s u r e d by e l e c t r o m a g n e t i c flowm e t e r and r a d i o a c t i v e m i c r o s p h e r e t e c n i q u e ~ r e s p e c t i v e l y . I n t e s t i n a l a b s o r p t i on of w a t e r , N a , K , C 1 , H C O 3 , w a s m e a s u r e d , i n v i v o , i n c l o s e d i l e a l loops of 12 dogs . I n t r a v e n o u s i n f u s i o n of SV (3, 5, 1 0 , 2 0 , 3 0 n g / k g / m i n ) p r o d u c e d a dose r e l a t e d i n c r e a s e of m e s e n t e r i c blood flow up to 3OOG c o n t r o l v a f u e s . M u c o s a l blood flow od ileum and colon was i n c r e a s e d , w h i l e m u s c o l a r blood flow w a s unaffected or slightly decreased.lntestinal absorption of w a t e r a n d e l e ctrolytes w a s r e v e r s e d to secretion~due to a significant d e c r e a s e in absorpti ve fluxes a n d increase in s e c r e t o r y fluxes.lt w a s c o n c l u d e d thaf S V di s p l a y s m a r k e d selectivity in p r o d u c i n g m e s e n t e r i c vasodilatation in the a p p a r e n t abs e n c e of other significant c a r d i o v a s c u l a r effects.The increase in m e s e n [ e r i c blood flow a p p e a r s to be restricted to s e c r e t o r y sites of intestinal m u c o s a a n d related to s e c r e t o r y fluxes of b i c a r b o n a t e s a n d w a ter.