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Orphanin FQ, but not dynorphin A, accelerates colonic transit in rats

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Presentation on theme: "Orphanin FQ, but not dynorphin A, accelerates colonic transit in rats"— Presentation transcript:

1 Orphanin FQ, but not dynorphin A, accelerates colonic transit in rats
Toku Takahashi, Yohei Mizuta, Chung Owyang  Gastroenterology  Volume 119, Issue 1, Pages (July 2000) DOI: /gast Copyright © 2000 American Gastroenterological Association Terms and Conditions

2 Fig. 1 OFQ (1 nmol · kg−1 · min−1) induced muscle contractions in the rat GI tract in vivo. Intravenous administration of OFQ caused contractions in the rat colon. OFQ did not significantly affect muscle contraction in the antrum or jejunum; its contractile effect on the ileum was transient. The muscarinic receptor agonist bethanechol (40 μg/kg), which was administered as a positive control, induced significant contractions in all regions of the GI tract. Results were reproducible in 5 rats. Gastroenterology  , 71-79DOI: ( /gast ) Copyright © 2000 American Gastroenterological Association Terms and Conditions

3 Fig. 2 OFQ (○; 10 pmol/kg to 3 nmol/kg) and dynorphin A (●; 100 pmol/kg to 30 nmol/kg) induced muscle contractions in the rat proximal colon in vivo. Intravenous administration of OFQ increased phasic contractions in the proximal colon. The threshold dose of OFQ was 10 pmol/kg. The maximal effect of OFQ, a 715% ± 89% increase over basal, was produced at a dose of 3 nmol/kg. The effect of dynorphin A on muscle contractions in the rat proximal colon was less potent (mean ± SE; n = 4). Gastroenterology  , 71-79DOI: ( /gast ) Copyright © 2000 American Gastroenterological Association Terms and Conditions

4 Fig. 3 Effects of (A) TTX and (B) L-NAME on OFQ (300 pmol/kg)-induced colonic contractions. TTX (36 μg/kg) significantly enhanced spontaneous colonic contractions. (A) OFQ failed to induce any additional contractions in the presence of TTX. (B) L-NAME (10 mg/kg) alone evoked significant colonic contractions, and OFQ stimulated additional contractions in the presence of L-NAME. Gastroenterology  , 71-79DOI: ( /gast ) Copyright © 2000 American Gastroenterological Association Terms and Conditions

5 Fig. 4 Effect of intracerebroventricular (ICV) administration of OFQ (3-300 pmol/kg) on motility in the rat proximal colon. In contrast to intravenous (IV) administration of OFQ, intracerebroventricular administration of OFQ (3-30 pmol/kg) failed to stimulate proximal colonic contractions. A higher concentration of OFQ (300 pmol/kg) evoked a small, transient increase in colonic contractions that may have been caused by a leakage of the peptide into the peripheral circulation. Results were reproducible in 4 rats. Gastroenterology  , 71-79DOI: ( /gast ) Copyright © 2000 American Gastroenterological Association Terms and Conditions

6 Fig. 5 Effects of OFQ (1-11), OFQ (1-12), OFQ (1-13), and OFQ (1-17) (300 pmol/kg) on muscle contractions in the rat proximal colon. OFQ (1-13) was as potent as OFQ (1-17), whereas OFQ (1-12) was 100 times less potent than OFQ (1-17). OFQ (1-11) had no effect on colonic contractions (mean ± SE; n = 4). Gastroenterology  , 71-79DOI: ( /gast ) Copyright © 2000 American Gastroenterological Association Terms and Conditions

7 Fig. 6 (A) OFQ (1 nmol · kg−1 · min−1) and (B) dynorphin A (100 nmol · kg−1 · min−1) induced colonic contractions in vivo. Continuous infusion of OFQ (1 nmol · kg−1 · min−1) and dynorphin A (100 nmol · kg−1 · min−1) for 2 minutes induced similar phasic contractions in the rat proximal colon (C1 and C2). In the mid and distal colon (C3 and C4), the 2 peptides evoked different modes of action. Large-amplitude contractions, which migrated from the mid (C3) to distal colon (C4), were observed during and after OFQ infusion. In contrast, dynorphin A induced simultaneous contractions throughout the entire rat colon. Results were reproducible in 6 rats. Gastroenterology  , 71-79DOI: ( /gast ) Copyright © 2000 American Gastroenterological Association Terms and Conditions

8 Fig. 7 (A) OFQ (1 nmol · kg−1 · min−1) and (B) dynorphin A (100 nmol · kg−1 · min−1) induced contractions in the mid and distal colon. During and after OFQ infusion, large-amplitude contractions migrated from the mid colon (C3) to the distal colon (C4 and C5). Computer analysis showed that the peak of OFQ-induced contraction at C4 occurred 2.4 ± 0.3 seconds after the peak contraction at C3 (n = 21 from 5 rats). Similarly, the peak of OFQ-induced contraction at C5 occurred 2.9 ± 0.4 seconds after the peak contraction at C4 (n = 21 from 5 rats; A). In contrast, the peak of dynorphin A–induced contraction occurred simultaneously at C3, C4, and C5. Each vertical line marks the peak of contraction observed at C3 induced by OFQ (1 nmol · kg−1 · min−1) and dynorphin A (100 nmol · kg−1 · min−1). Results were reproducible in 5 rats. Gastroenterology  , 71-79DOI: ( /gast ) Copyright © 2000 American Gastroenterological Association Terms and Conditions

9 Fig. 8 OFQ (1-10 nmol · kg−1 · min−1) induced propulsive contractions in the mid and distal colon. OFQ induced large amplitude contractions in the mid colon (C3), which migrated to recording sites in the distal colon (C4 and C5). These migrating contractions were dose-dependent of OFQ (1-10 nmol · kg−1 · min−1). Results were reproducible in 5 rats. Gastroenterology  , 71-79DOI: ( /gast ) Copyright © 2000 American Gastroenterological Association Terms and Conditions

10 Fig. 9 Effects of OFQ (1-3 nmol/kg) and dynorphin A ( nmol/kg) on colonic transit in conscious rats, expressed as the geometric center. Administration of OFQ (1-3 nmol/kg) accelerated colonic transit, compared with the saline-injected group. In contrast, dynorphin A ( nmol/kg) delayed colonic transit (n = 4, mean ± SE; *P < 0.05, **P < 0.01 vs. the saline-injected group). Gastroenterology  , 71-79DOI: ( /gast ) Copyright © 2000 American Gastroenterological Association Terms and Conditions


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