Urocortin 2 Acts Centrally to Delay Gastric Emptying through Sympathetic Pathways while CRF and Urocortin 1 Inhibitory Actions Are Vagal Dependent in Rats
Abstract
We characterized the influence of the selective corticotropin-releasing factor 2 (CRF(2)) receptor agonist human urocortin 2 (Ucn 2), injected intracisternally, on gastric emptying and its mechanism of action compared with intracisternal CRF or urocortin (Ucn 1) in conscious rats. The methylcellulose phenol red solution was gavaged 20 min after peptide injection, and gastric emptying was measured 20 min later. The intracisternal injection of Ucn 2 (0.1 and 1 microg) and Ucn 1 (1 microg) decreased gastric emptying to 37.8 +/- 6.9%, 23.1 +/- 8.6%, and 21.6 +/- 5.9%, respectively, compared with 58.4 +/- 3.8% after intracisternal vehicle. At lower doses, Ucn 2 (0.03 microg) and Ucn 1 (0.1 microg) had no effect. The CRF(2) antagonist astressin(2)-B (3 microg ic) antagonized intracisternal Ucn 2 (0.1 microg) and CRF (0.3 microg)-induced inhibition of gastric emptying. Vagotomy enhanced intracisternal Ucn 2 (0.1 or 1 microg)-induced inhibition of gastric emptying compared with sham-operated group, whereas it blocked intracisternal CRF (1 microg) inhibitory action (45.5 +/- 8.4% vs. 9.7 +/- 9.7%). Sympathetic blockade by bretylium prevented intracisternal and intracerebroventricular Ucn 2-induced delayed gastric emptying, whereas it did not influence intravenous Ucn 2-, intracisternal CRF-, and intracisternal Ucn 1-induced inhibition of gastric emptying. Prazosin abolished the intracisternal Ucn 2 inhibitory effect, whereas yohimbine and propranolol did not. None of the pretreatments modified basal gastric emptying. These data indicate that intracisternal Ucn 2 induced a central CRF(2)-mediated inhibition of gastric emptying involving sympathetic alpha(1)-adrenergic mechanisms independent from the vagus contrasting with the vagal-dependent inhibitory actions of CRF and Ucn 1.
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In the hypothalamus, PFOS caused upregulation of urocortin 2, an endogenous ligand for CRFR2 that suppresses feeding behavior and inhibits gastric emptying.
“In the hypothalamus, PFOS caused upregulation of urocortin 2, an endogenous ligand for corticotropin releasing factor receptor 2 (CRFR2) that has been shown to suppress feeding behavior and inhibit gastric emptying”
From A Critical Review and Meta-Analysis of Impacts of Per- and Polyfluorinated Substances on the Brain and Behavior (2022) · cites this paper as Czimmer et al., 2006
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BackgroundTargeting the gut to treat multiple sclerosis
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BackgroundPreproghrelin‐derived Peptide, Obestatin, Fails to Influence Food Intake in Lean or Obese Rodents
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“CRF, Ucn 1 and nesfatin-1 reduce food intake and gastric emptying after central as well as peripheral injection [16, 43, 53, 56] and we could recently show that central nesfatin-1 exerts its anorexigenic effect via a CRF2 receptor-dependent pathway [60].”
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“Case in point, Ucn 2 (CRF 2 preferring), CRF (CRF 1 preferring) and Ucn 1 (non-selective) act centrally to delay gastric emptying [78,79] .”
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Kimura, T., Amano, T., Uehara, H., Ariga, H., Ishida, T., Torii, A., Tajiri, H., Matsueda, K., & Yamato, S. (2007) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00066.2007 · Cited by 37 · see citing works
“Selective CRF1 receptor antagonist antalarmin and selective CRF2 receptor antagonist astressin2-B were used in supramaximal doses (8, 26).”
MethodPerfluorooctane Sulfonate Influences Feeding Behavior and Gut Motility via the Hypothalamus
Asakawa, A., Toyoshima, M., Fujimiya, M., Harada, K., Ataka, K., Inoue, K., & Koizumi, A. (2007) · International Journal of Molecular Medicine · doi:10.3892/ijmm.19.5.733 · Cited by 33 · see citing works
“delays gastric emptying (Hsu and Hsueh 2001; Czimmer et al. 2006 ).”
Liu, S., Ren, W., Qu, M., Bishop, G. A., Wang, G., Wang, X., Xia, Y. L., & Wood, J. (2009) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2009.00516.x · Cited by 33 · see citing works
“CRF, Ucn1 and Ucn2, when injected into the brain, act at the CRF2 receptor subtype to inhibit gastric emptying (Kihara et al., 2001; Chen et al., 2002; Martinez et al., 2004; Czimmer et al., 2006).”
BackgroundStengel, A., Goebel‐Stengel, M., Wang, L., Shaikh, A., Lambrecht, N. W. G., Rivier, J., & Taché, Y. (2011) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00018.2011 · Cited by 33 · see citing works
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“The abdominal cavity was opened, gastric pylorus and cardia were clamped, and the stomach removed and gastric emptying assessed as detailed previously [11].”
MethodAmyloid Beta Peptide Slows Down Sensory-Induced Hippocampal Oscillations
Peña‐Ortega, F., & Bernal‐Pedraza, R. (2012) · International Journal of Peptides · doi:10.1155/2012/236289 · Cited by 29 · see citing works
“It has been found that intracerebroventricular and intracisternal administration of the same substance do not always produce the same effect, probably due to differences in the brain structures preferentially reached by the injection in those sites, as well as to the different concentrations of the injected substance…”
BackgroundHagiwara, S., Kaushal, E., Paruthiyil, S., Pasricha, P. J., Hasdemir, B., & Bhargava, A. (2018) · PLoS ONE · doi:10.1371/journal.pone.0203704 · Cited by 28 · see citing works
“While central CRF- and vagal nerve-dependent mechanisms [21, 22] contributed to symptoms in FGID models, the role of gastric CRF in FD models has not been demonstrated.”
BackgroundResultGastrointestinal peptides controlling body weight homeostasis
Zerón, H. M., López, M., & Diéguez, C. (2007) · General and Comparative Endocrinology · doi:10.1016/j.ygcen.2007.11.009 · Cited by 28 · see citing works
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“Previous studies have shown that both urocortins 2 and 3 potently suppress food intake and delay gastric emptying (Hsu and Hsueh, 2001; Ohata and Shibasaki, 2004; Czimmer et al., 2006).”
ResultDoes stress induce bowel dysfunction?
Chang, Y.-M., Zaatari, M. E., & Kao, J. Y. (2014) · Expert Review of Gastroenterology & Hepatology · doi:10.1586/17474124.2014.911659 · Cited by 23 · see citing works
“For example, urocortin 1 is predominantly a CRF1 ligand, and urocortin 2 is mainly a CRF2 ligand but injection of either urocortin into the CNS resulted in delayed gastric emptying [3,4].”
BackgroundChapter 1 Recent Advances in Corticotropin-Releasing Factor Receptor Antagonists
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BackgroundCentrally administered urocortin 3 inhibits food intake and gastric emptying in mice
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Peripheral α2-β1 adrenergic interactions mediate the ghrelin response to brain urocortin 1 in rats
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InfluentialUrocortins are present in the rat testis
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Do urocortins have a role in treating cardiovascular disease?
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Molecular Signaling in the Gut–Brain Axis in Stress
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Novel Management of Heart Failure
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- Authors
- Czimmer, J., Million, M., & Taché, Y.
- Affiliations
- University of California, Los Angeles (US)
- Venue
- American Journal of Physiology-Gastrointestinal and Liver Physiology
- Publisher
- American Physiological Society
- Published
- 2006-03
- Volume
- 290
- Issue
- 3
- Pages
- G511-G518
- ISSN
- 0193-1857 (ISSN-L)
- 1522-1547
- OpenAlex
- W2056625607
- Cited by
- 59
- References
- 52
- Citations by year
- 2025: 1 · 2024: 1 · 2023: 1 · 2022: 1 · 2021: 2 · 2020: 4 · 2019: 1 · 2018: 5 · 2017: 2 · 2016: 2 · 2015: 3 · 2014: 4 · 2013: 3 · 2012: 3
- FWCI
- 1.56
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Physiology-Gastrointestinal and Liver Physiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (DK 41301, R01DK033061, R01 DK 33061, P30DK041301)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Keywords
- urocortin 2, urocortin 1, corticotropin-releasing factor, gastric emptying, vagus nerve, sympathetic nervous system, alpha1-adrenoceptors, vagotomy, prazosin, central nervous system, stress response, gastrointestinal motility, rats, sympathoinhibition
- MeSH terms
- Adrenergic alpha-Antagonists, Adrenergic beta-Antagonists, Animals, Bretylium Compounds, Corticotropin-Releasing Hormone, Gastric Emptying, Humans, Male, Peptide Fragments, Prazosin, Sympathetic Nervous System, Vagotomy, Vagus Nerve, Yohimbine, Rats, Urocortins
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