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 HighWire Citing Articles via Google Scholar Google Scholar Articles by Tsuda, A. Articles by Sumikawa, K. Search for Related Content PubMed PubMed Citation Articles by Tsuda, A. Articles by Sumikawa, K. Related Collections Pharmacology

---

ANESTHETIC PHARMACOLOGY

A Dose-Response Study of Anticholinesterase Drugs on Contractile and Phosphatidylinositol Responses of Rat Trachea

Department of Anesthesiology, Nagasaki University School of Medicine, Nagasaki, Japan

Address correspondence and reprint requests to Atsushi Tsuda, MD, Department of Anesthesiology, Nagasaki University School of Medicine, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan. Address e-mail to d397049x{at}stcc.nagasaki-u.ac.jp

We investigated whether anticholinesterase drugs in large doses inhibit muscarinic receptors of airway smooth muscle. In vitro measurements of isometric tension and [³H]inositol monophosphate (IP₁) that formed were conducted by using rat tracheal rings or slices. Neostigmine and pyridostigmine caused muscular contraction and IP₁ accumulation in small doses (10 µM and 100 µM, respectively), but they attenuated muscular contraction and IP₁ accumulation in larger doses (1000 µM). Edrophonium did not affect the smooth muscle tone and IP₁ levels. Neostigmine, pyridostigmine, and edrophonium attenuated the carbachol (5.5 µM)-induced smooth muscle contraction and IP₁ accumulation, when administered in large doses (1000 µM). The attenuation of contraction by neostigmine at large doses was not affected by methoctramine, an M₂ muscarinic receptor antagonist, but was reversed by washing with fresh Krebs-Henseleit solution. The results suggest that anticholinesterase drugs have dual effects on the tension and phosphatidylinositol responses of rat trachea. Large doses of anticholinesterase drugs cause airway smooth muscle relaxation, which may be seen in patients with myasthenia gravis who have received excessive anticholinesterase therapy.

Implications: Neostigmine and pyridostigmine, but not edrophonium, have dual effects on the tension and phosphatidylinositol responses of rat trachea. Large doses of anticholinesterase drugs cause airway smooth muscle relaxation, which may be seen in patients with myasthenia gravis who have received excessive anticholinesterase therapy.

This article has been cited by other articles:

				O. Shibata, M. Saito, M. Yoshimura, M. Yamaguchi, K. Nishioka, T. Makita, and K. Sumikawa Anticholinesterase drugs stimulate smooth muscle contraction of the rat trachea through the rho-kinase pathway. Anesth. Analg., April 1, 2006; 102(4): 1121 - 1126. [Abstract] [Full Text] [PDF]

				M. Saito, O. Shibata, M. Yamaguchi, M. Yoshimura, T. Makita, N. Harada, M. Niwa, and K. Sumikawa Metoclopramide Causes Airway Smooth Muscle Relaxation Through Inhibition of Muscarinic M3 Receptor in the Rat Trachea Anesth. Analg., May 1, 2004; 98(5): 1325 - 1329. [Abstract] [Full Text] [PDF]

				O. Shibata, M. Saito, M. Yoshimura, M. Yamaguchi, T. Makita, and K. Sumikawa Interactions of Edrophonium with Neostigmine in the Rat Trachea Anesth. Analg., October 1, 2003; 97(4): 1059 - 1063. [Abstract] [Full Text] [PDF]

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