Journal article
Norepinephrine Has Dual Effects on Human Colonic Contractions Through Distinct Subtypes of Alpha 1 Adrenoceptors
Cellular and molecular gastroenterology and hepatology, Vol.10(3), pp.658-671.e1
2020
DOI: 10.1016/j.jcmgh.2020.04.015
PMCID: PMC7474159
PMID: 32376421
Abstract
Colonic musculature contain smooth muscle cells (SMC), interstitial cells of Cajal (ICC), and platelet-derived growth factor receptor α
cells (PDGFRα
cells), which are electrically coupled and operate together as the SIP syncytium. PDGFRα
cells have enriched expression of small conductance Ca
-activated K
(SK) channels. Purinergic enteric neural input activates SK channels in PDGFRα
cells, hyperpolarizes SMC, and inhibits colonic contractions. Recently we discovered that PDGFRα
cells in mouse colon have enriched expression of α1A adrenoceptors (ARs), which coupled to activation of SK channels and inhibited colonic motility, and α1A ARs were principal targets for sympathetic regulation of colonic motility. Here we investigated whether PDGFRα
cells in human colon express α1A ARs and share the roles as targets for sympathetic regulation of colonic motility.
Isometric tension recording, intracellular recording, and Ca
imaging were performed on muscles of the human colon. Responses to α1 ARs agonists or electric field stimulation with AR antagonists and neuroleptic reagents were studied.
Exogenous or endogenous norepinephrine released from nerve fibers inhibited colonic contractions through binding to α1A ARs or enhanced colonic contractions by acting on α1D ARs. Inhibitory responses were blocked by apamin, an antagonist of SK channels. Phenylephrine, α1 AR agonists, or norepinephrine increased intracellular [Ca
] in PDGFRα
cells, but not in ICC, and hyperpolarized SMCs by binding to α1 ARs expressed by PDGFRα
cells.
Human colonic contractions are inhibited by α1A ARs expressed in PDGFRα
cells and activated by α1D ARs expressed in SMC.
Details
- Title: Subtitle
- Norepinephrine Has Dual Effects on Human Colonic Contractions Through Distinct Subtypes of Alpha 1 Adrenoceptors
- Creators
- Masaaki Kurahashi - University of Nevada RenoYoshihiko Kito - Saga UniversityMasayasu Hara - Nagoya City UniversityHiromitsu Takeyama - Nagoya City UniversityKenton M Sanders - University of Nevada RenoHikaru Hashitani - Nagoya City University
- Resource Type
- Journal article
- Publication Details
- Cellular and molecular gastroenterology and hepatology, Vol.10(3), pp.658-671.e1
- DOI
- 10.1016/j.jcmgh.2020.04.015
- PMID
- 32376421
- PMCID
- PMC7474159
- ISSN
- 2352-345X
- eISSN
- 2352-345X
- Grant note
- R01 DK091336 / NIDDK NIH HHS
- Language
- English
- Date published
- 2020
- Academic Unit
- Internal Medicine
- Record Identifier
- 9984359695102771
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