Makwana, R; Loy, J; Adebibe, M; Devalia, K; Andrews, PL; Sanger, GJ
(2021)
Copeptin, a surrogate marker of arginine8 vasopressin, has no ability to modulate human and mouse gastric motility.
Eur J Pharmacol, 892.
p. 173740.
ISSN 1879-0712
https://doi.org/10.1016/j.ejphar.2020.173740
SGUL Authors: Andrews, Paul Lyn Rodney
Abstract
Copeptin, a glycosylated peptide fragment derived from the C-terminal region of the precursor of arginine8 vasopressin (AVP), is co-secreted with AVP in equimolar amounts. Elevated plasma AVP modulates gastric motility so we investigated whether copeptin had a similar effect. Copeptin (10-9-10-7M), and AVP (10-12-10-5M), were evaluated for their ability to modulate spontaneous and electrically-evoked (EFS) contractions of human proximal and distal gastric circular muscle in vitro. Similar experiments were performed on the mouse stomach and we re-examined the published effect of copeptin on the mouse aorta. In the presence of tetrodotoxin (10-6M), atropine (10-6M) and L-NAME (3 × 10-4M), human proximal and distal stomach muscle contracted spontaneously and rhythmically as did mouse distal stomach. Copeptin (10-9-10-7M), had no effect on baseline muscle tone or myogenic spontaneous contractions of either human or mouse stomach. However, AVP concentration-dependently increased tone, amplitude and frequency of contractions in both regions of human stomach with similar potency (pEC50 9.0-9.5; n = 4) and threshold concentration (10-11-10-10M). AVP was similarly active in the mouse stomach. EFS-evoked cholinergic contractions (human and mouse) were unaffected by both peptides EFS-evoked relaxations of mouse stomach were unaffected by copeptin. In sub-maximally contracted mouse aorta the elevated tone was unaffected by copeptin (10-7M) (cf. previously published study) but was reduced by carbachol (10-6M) and sodium nitroprusside (10-3M). We conclude that in contrast to AVP, copeptin over a concentration range reported in the plasma has no direct ability to modulate the motility of the human and mouse stomach.
Item Type: |
Article
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Additional Information: |
© 2020. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ |
Keywords: |
Antidiuretic hormone, Arginine(8) vasopressin, Copeptin, Gastric motility human stomach, Nausea, Pharmacology & Pharmacy, Behavioral Science & Comparative Psychology, 1115 Pharmacology and Pharmaceutical Sciences, 0801 Artificial Intelligence and Image Processing, 1701 Psychology, 1702 Cognitive Sciences |
SGUL Research Institute / Research Centre: |
Academic Structure > Molecular and Clinical Sciences Research Institute (MCS) |
Journal or Publication Title: |
Eur J Pharmacol |
ISSN: |
1879-0712 |
Language: |
eng |
Dates: |
Date | Event |
---|
5 February 2021 | Published | 18 November 2020 | Published Online | 16 November 2020 | Accepted |
|
Publisher License: |
Creative Commons: Attribution-Noncommercial-No Derivative Works 4.0 |
PubMed ID: |
33220268 |
![](http://static.pubmed.gov/portal/portal3rc.fcgi/2745237/img/27842) |
Go to PubMed abstract |
URI: |
https://openaccess.sgul.ac.uk/id/eprint/112840 |
Publisher's version: |
https://doi.org/10.1016/j.ejphar.2020.173740 |
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