JOURNAL HOME CME HOME THIS MONTH PAST ISSUES ETOC COLLECTIONS AUTHORS REVIEWERS EDITORIAL BOARD FEEDBACK RSS HELP
		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Saito, M. Articles by Sumikawa, K. Search for Related Content PubMed PubMed Citation Articles by Saito, M. Articles by Sumikawa, K. Related Collections Mechanisms Pharmacology

---

ANESTHETIC PHARMACOLOGY

Metoclopramide Causes Airway Smooth Muscle Relaxation Through Inhibition of Muscarinic M₃ Receptor in the Rat Trachea

Masataka Saito, MD^*, Osamu Shibata, MD^*, Masakazu Yamaguchi, MD^*, Maki Yoshimura, MD^*, Tetsuji Makita, MD^*, Noboru Harada, MD^*, Masami Niwa, MD, and Koji Sumikawa, MD^*

Departments of *Anesthesiology and Pharmacology 1, Nagasaki University School of Medicine, Nagasaki, Japan

Address correspondence and reprint requests to Masataka Saito, MD, Department of Anesthesia, Kitakyushu-city Yahata Hospital, 4-18-1 Nishihonmachi, Yahatahigashi, Kitakyushu 805-0061, Japan. Address e-mail to saito{at}yahatahp.jp

Although metoclopramide, often used as an antiemetic, is reported to have an anticholinesterase action, the effect on airway smooth muscle remains unclear. We investigated the effect of metoclopramide on the contraction, phosphatidylinositol response, and binding affinity of muscarinic M₃ receptors in rat trachea preparations. Male Wistar rats were anesthetized and their tracheas excised and chopped into 3-mm-wide rings, 1-mm-wide slices, or frozen 10-µm-thick sections. Contraction was induced with 0.55 µM carbachol (CCh) and, 30 min later, metoclopramide (10 µM to 1 mM) was added. The slices were incubated with ³[H]myo-inositol, 0.55 µM CCh, and metoclopramide, and the formation of ³[H] inositol monophosphate was measured. A radioligand binding study was conducted to examine the effects of metoclopramide using [³H] 4-diphenylacetoxy-N-methyl-piperidine methobromide (4-DAMP), a muscarinic M₃ receptor antagonist, in sections of the trachea. Metoclopramide concentration dependently attenuated CCh-induced contraction and inositol monophosphate accumulation, and also attenuated the binding affinity of 4-DAMP to muscarinic M₃ receptors. The 50% inhibitory concentration of metoclopramide against the binding affinity of 4-DAMP to muscarinic M₃ receptors of rat trachea was 24 µM. These findings suggest that the attenuation by metoclopramide of CCh-induced contraction and phosphatidylinositol response may be mediated through the muscarinic M₃ receptors.

IMPLICATIONS: We investigated the effect of metoclopramide on the contraction, phosphatidylinositol response, and binding affinity of muscarinic M₃ receptors in rat trachea preparations. Our findings suggest that the attenuation by metoclopramide of carbachol-induced contraction and phosphatidylinositol response may be mediated through the muscarinic M₃ receptors.

Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999