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 ISI Web of Science (6) Citing Articles via Google Scholar Google Scholar Articles by Shiraishi, M. Articles by Shigematsu, A. Search for Related Content PubMed PubMed Citation Articles by Shiraishi, M. Articles by Shigematsu, A. Related Collections Pharmacology

---

ANESTHETIC PHARMACOLOGY

A Neurosteroid Anesthetic, Alphaxalone, Inhibits Nicotinic Acetylcholine Receptors in Cultured Bovine Adrenal Chromaffin Cells

Munehiro Shiraishi, MD^*, Izumi Shibuya, PhD, Kouichiro Minami, MD PhD^*, Yasuhito Uezono, MD PhD, Takashi Okamoto, MD^*, Nobuyuki Yanagihara, PhD, Susumu Ueno, MD PhD, Yoichi Ueta, MD PhD, and Akio Shigematsu, MD PhD^*

Departments of *Anesthesiology, Physiology, and Pharmacology, University of Occupational and Environmental Health, School of Medicine, Kitakyushu; and Department of Second Pharmacology, Nagasaki University, School of Medicine, Nagasaki, Japan

Address correspondence and reprint requests to Kouichiro Minami, MD, PhD, Department of Anesthesiology, University of Occupational and Environmental Health, School of Medicine, 1-1 Iseigaoka, Yahatanishiku, Kitakyushu 807-8555, Japan. Address e-mail to kminami{at}med.uoeh-u.ac.jp

Several lines of evidence suggest that nicotinic acetylcholine receptors (nAChRs) are a target of general anesthetics. Alphaxalone (5-pregnan-3-ol-11, 20-dion) is a neurosteroid, which was used clinically for anesthesia, but its effects on the function of nAChRs have not been well investigated. We examined the effects of alphaxalone on nAChRs in cultured bovine adrenal chromaffin cells. We studied the effects of alphaxalone on nicotine-induced increases in the cytosolic Ca²⁺ concentration ([Ca²⁺]_i) and on membrane currents using Ca²⁺-imaging and whole-cell patch-clamp techniques, respectively, in these cells. We also examined the effects of alphaxalone on -aminobutyric acid A receptors in the same cells and compared them with the effects on nAChRs. Alphaxalone (0.1–100 µM) inhibited nicotine-induced [Ca²⁺]_i increases in a concentration-dependent manner. Alphaxalone inhibited high K⁺-induced [Ca²⁺]_i increases, but the inhibition was observed only at 100 µM. In voltage-clamp experiments using negative holding potentials, alphaxalone (0.1–100 µM) itself induced inward currents, which were abolished by the -aminobutyric acid A receptor antagonist picrotoxin. Alphaxalone also inhibited nicotine-induced inward currents, and the inhibition was unaffected by picrotoxin. We conclude that alphaxalone, at anesthetic concentrations, inhibits nAChRs in adrenal chromaffin cells. Alphaxalone may affect the sympathetic and other nervous systems via inhibition of nAChRs.

IMPLICATIONS: Alphaxalone inhibits the function of nAChRs at clinically relevant concentrations in adrenal chromaffin cells. Thus, the present findings may provide some information for understanding the anesthetic mechanism of alphaxalone.

This article has been cited by other articles:

				G. A. F. Nievas, F. J. Barrantes, and S. S. Antollini Modulation of Nicotinic Acetylcholine Receptor Conformational State by Free Fatty Acids and Steroids J. Biol. Chem., August 1, 2008; 283(31): 21478 - 21486. [Abstract] [Full Text] [PDF]

				B. M. Stell, S. G. Brickley, C. Y. Tang, M. Farrant, and I. Mody Neuroactive steroids reduce neuronal excitability by selectively enhancing tonic inhibition mediated by {delta} subunit-containing GABAA receptors PNAS, November 25, 2003; 100(24): 14439 - 14444. [Abstract] [Full Text] [PDF]

				M. Shiraishi, K. Minami, I. Shibuya, Y. Uezono, J. Ogata, T. Okamoto, O. Murasaki, M. Kaibara, Y. Ueta, and A. Shigematsu The Inhibitory Effects of Alphaxalone on M1 and M3 Muscarinic Receptors Expressed in Xenopus Oocytes Anesth. Analg., August 1, 2003; 97(2): 449 - 455. [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