C-type natriuretic peptide specifically acts on the pylorus and large intestine in mouse gastrointestinal tract

Chizuru Sogawa, Hidekatsu Wakizaka, Winn Aung, Zhao Hui Jin, Atsushi B. Tsuji, Takako Furukawa, Tetsuo Kunieda, Tsuneo Saga

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

C-type natriuretic peptide (CNP) exerts its main biological effects by binding to natriuretic peptide receptor B (NPR-B), a membrane-bound guanylyl cyclase receptor that produces cyclic guanosine monophosphate (cGMP). CNP is known to cause gastrointestinal (GI) smooth muscle relaxation. Experimental evidence suggests a connection between CNP signaling and GI function, with reactive regions in the GI tract possibly affecting transit; however, this relation has not yet been conclusively shown. Here, we show that CNP plays important region-specific roles in the GI tract of mice. We found that treatment with CNP (1 or 2 mg/kg) increased transient cGMP production in the pylorus, colon, and rectum, with the higher dose (2 mg/kg) enhancing gastric emptying in mice; this increase in cGMP levels was however absent in NPR-B-deficient short-limbed dwarfism (SLW) mouse. Furthermore, we found that NPR-B is highly expressed in the pylorus, colon, and rectum, being localized to nerve fibers and to the nuclei and cytoplasm of smooth muscle cells of the GI tract and blood vessels. Our in vivo findings showed that NPR-B-mediated cGMP production after CNP administration specifically acted on the pylorus, colon, and rectum and contributed to gastric emptying. CNP may thus be a potential therapeutic agent for GI motility/transit disorders such as ileus and pyloric stenosis.

Original languageEnglish
Pages (from-to)172-179
Number of pages8
JournalAmerican Journal of Pathology
Volume182
Issue number1
DOIs
Publication statusPublished - Jan 2013

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C-Type Natriuretic Peptide
Large Intestine
Pylorus
Gastrointestinal Tract
Cyclic GMP
Rectum
Colon
Gastric Emptying
Guanylate Cyclase-Coupled Receptors
Pyloric Stenosis
Gastrointestinal Transit
Dwarfism
Gastrointestinal Motility
Muscle Relaxation
Ileus
Nerve Fibers
Smooth Muscle Myocytes
Smooth Muscle
Blood Vessels
Cytoplasm

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

C-type natriuretic peptide specifically acts on the pylorus and large intestine in mouse gastrointestinal tract. / Sogawa, Chizuru; Wakizaka, Hidekatsu; Aung, Winn; Jin, Zhao Hui; Tsuji, Atsushi B.; Furukawa, Takako; Kunieda, Tetsuo; Saga, Tsuneo.

In: American Journal of Pathology, Vol. 182, No. 1, 01.2013, p. 172-179.

Research output: Contribution to journalArticle

Sogawa, Chizuru ; Wakizaka, Hidekatsu ; Aung, Winn ; Jin, Zhao Hui ; Tsuji, Atsushi B. ; Furukawa, Takako ; Kunieda, Tetsuo ; Saga, Tsuneo. / C-type natriuretic peptide specifically acts on the pylorus and large intestine in mouse gastrointestinal tract. In: American Journal of Pathology. 2013 ; Vol. 182, No. 1. pp. 172-179.
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