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Serotonin released from intestinal enterochromaffin cells mediates luminal non– cholecystokinin-stimulated pancreatic secretion in rats  Ying Li, Yibai.

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Presentation on theme: "Serotonin released from intestinal enterochromaffin cells mediates luminal non– cholecystokinin-stimulated pancreatic secretion in rats  Ying Li, Yibai."— Presentation transcript:

1 Serotonin released from intestinal enterochromaffin cells mediates luminal non– cholecystokinin-stimulated pancreatic secretion in rats  Ying Li, Yibai Hao, Jinxia Zhu, Chung Owyang  Gastroenterology  Volume 118, Issue 6, Pages (June 2000) DOI: /S (00) Copyright © 2000 American Gastroenterological Association Terms and Conditions

2 Fig. 1 Pancreatic protein secretion in response to chopped rodent chow in conscious rats. The CCK-A receptor antagonist L364,718 (2, 0.5 mg/kg) produced a 54% inhibition, whereas a combination of L364,718, the 5-HT3 receptor antagonist ICS (250 μg/kg IV) and the 5-HT2 receptor antagonist ketanserin (250 μg/kg IV) (●) produced a 94% inhibition of rodent chow–stimulated pancreatic secretion. ○, Vehicle. Values are mean ± SE for 6 rats for each time point. *P < Gastroenterology  , DOI: ( /S (00) ) Copyright © 2000 American Gastroenterological Association Terms and Conditions

3 Fig. 2 Duodenal perfusion of (A) 500 mOsm NaCl and (B) 300 mmol/L maltose caused a 52% and a 70% increase in protein output over basal, respectively. (C and D) Stroking by gentle movement of a small intraluminal applicator against the mucosa caused an 87% increase (3 strokes/min) and a 200% increase (10 strokes/min) in pancreatic protein output over basal. ○, Vehicle; ▴, afferent rootlet section. Vagal afferent rootlet section eliminated pancreatic protein secretion evoked by these stimuli. Values are mean ± SE for 6 rats in each group. *P < Gastroenterology  , DOI: ( /S (00) ) Copyright © 2000 American Gastroenterological Association Terms and Conditions

4 Fig. 3 Pancreatic protein output in response to intraduodenal infusion of hyperosmolar NaCl, maltose, and light stroking of the mucosa. Rats were pretreated with 5-HT receptor antagonists. Pretreatment with the 5-HT3 antagonist ICS (250 μg/kg IV) resulted in a significant inhibition of pancreatic protein secretion evoked by intraduodenal perfusion of hyperosmolar (A) NaCl and (B) maltose. (C) In contrast, ICS induced a 20% inhibition of pancreatic secretion stimulated by mucosal stroking, and the 5-HT1p antagonist 5-HTP-DP-acetyl (1 mg/kg IV) had no effect. (A-C) ○, Vehicle; ●, 5-HTP-DP-acetyl; 2, ICS (D) Administration of ICS plus the 5-HT2 antagonist ketanserin (▴, 250 μg/kg IV) significantly inhibited pancreatic secretion stimulated by mucosal stroking. ▵, Vehicle. Gastroenterology  , DOI: ( /S (00) ) Copyright © 2000 American Gastroenterological Association Terms and Conditions

5 Fig. 4 Effect of PCPA on pancreatic protein secretion in response to intraduodenal infusion of (A) hyperosmolar NaCl, (B) maltose, and (C) mucosal stroking. IP administration of the 5-HT synthesis inhibitor PCPA (●, 500 mg/kg, over 2 consecutive days) completely eliminated pancreatic secretion evoked by intraduodenal hyperosmolar NaCl, maltose, and mucosal stroking. ○, Vehicle. Gastroenterology  , DOI: ( /S (00) ) Copyright © 2000 American Gastroenterological Association Terms and Conditions

6 Fig. 5 (A) In conscious rats, intraduodenal administration of hyperosmolar NaCl (2) and maltose (○) produced an 86% increase and a 92% increase in pancreatic protein secretion over basal, respectively. Administration of the 5-HT synthesis inhibitor PCPA (500 mg/kg, over 2 consecutive days) produced a 90% inhibition of pancreatic secretion evoked by intraduodenal hyperosmolar NaCl (■) and maltose (●). (B) Pretreatment with the 5-HT3 antagonist ICS (250 μg/kg IV) abolished pancreatic protein secretion evoked by intraduodenal perfusion of hyperosmolar NaCl and maltose in conscious rats. (A) ○, Vehicle + maltose; ●, PCPA + maltose; 2, vehicle mOsm NaCl; ■, PCPA mOsm NaCl. (B) ○, Vehicle + maltose; ●, ICS maltose; 2, vehicle mOsm NaCl; ■, ICS mOsm NaCl. Gastroenterology  , DOI: ( /S (00) ) Copyright © 2000 American Gastroenterological Association Terms and Conditions

7 Fig. 6 Intraduodenal administration of (A) hyperosmolar NaCl, (B) maltose, and (C) light mucosal stroking produced 52%, 70%, and 200% increases in pancreatic protein secretion over basal, respectively. In contrast to pretreatment with PCPA, ICV administration of 5,7-DHT (●, 200 μg in 5 μL) failed to inhibit luminal stimuli–induced pancreatic secretion. ○, Vehicle. Gastroenterology  , DOI: ( /S (00) ) Copyright © 2000 American Gastroenterological Association Terms and Conditions

8 Fig. 7 IP administration of 5,7-DHT (●, 300 mg/kg) did not affect pancreatic secretion stimulated by intraduodenal infusion of (A) hyperosmolar NaCl, (B) maltose, and (C) light mucosal stroking. ○, Vehicle. Gastroenterology  , DOI: ( /S (00) ) Copyright © 2000 American Gastroenterological Association Terms and Conditions

9 Fig. 8 (A) Effect of ICV 5,7-DHT on hypothalamic monoamine concentrations in rats. ICV 5,7-DHT treatment decreased the hypothalamic 5-HT to 8.5% of control level. In contrast, dopamine (DA) and noradrenaline (NA) levels were not affected ▨, 200 μg ICV 5,7-DHT; 2, vehicle. (B) Effect of PCPA on the concentration of 5-HT in the duodenal mucosa in rats. PCPA induced a profound depletion of 5-HT levels. (C) In contrast, noradrenaline levels were not affected. P < Gastroenterology  , DOI: ( /S (00) ) Copyright © 2000 American Gastroenterological Association Terms and Conditions


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