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Anesth Analg 2005;101:1681-1688
© 2005 International Anesthesia Research Society
doi: 10.1213/01.ANE.0000184137.37687.B7

ANESTHETIC PHARMACOLOGY

Peripheral N-Methyl-d-Aspartate Receptors Modulate Nonadrenergic Noncholinergic Lower Esophageal Sphincter Relaxation in Rabbits

Atsushi Kohjitani, DDS, PhD, Makoto Funahashi, DDS, PhD, Takuya Miyawaki, DDS, PhD, Motohiko Hanazaki, MD, PhD, Ryuji Matsuo, DDS, PhD, and Masahiko Shimada, DDS, PhD

Departments of Dental Anesthesiology and Anesthesiology and Resuscitology, Okayama University Hospital of Medicine and Dentistry, and Departments of Dental Anesthesiology and Oral Physiology, Okayama University Graduate School of Medicine and Dentistry

Address correspondence and reprint requests to Atsushi Kohjitani, DDS, PhD, Department of Dental Anesthesiology, Okayama University Hospital of Medicine and Dentistry, 2–5–1 Shikata-cho, Okayama 700–8525, Japan. Address e-mail to atsushik{at}md.okayama-u.ac.jp.

We investigated the role of peripheral N-methyl-d-aspartate (NMDA) receptors in the myenteric plexus in mediating nonadrenergic noncholinergic (NANC) nitrergic relaxation of the lower esophageal sphincter (LES). Isometric contraction of LES strips from Japanese White rabbits was measured. NANC relaxation was induced by KCl (30 mM) in the presence of atropine and guanethidine. The concentration of 3',5'-cyclic guanosine monophosphate (cGMP) was measured using a radioimmunoassay. The muscle strips were exposed to diethyldithiocarbamic acid (DETCA; 3 mM) to inactivate Cu/Zn superoxide dismutase. MK801 (5-methyl-10,11-dihydroxy-5H-dibenzo(a,d)cyclohepten-5,10-imine) inhibited NANC relaxation in a concentration-dependent manner (EC50 = 1.5 x 10–5 M), accompanied by a decrease in cGMP production. NMDA induced a concentration-dependent relaxation, which was antagonized by MK801. NMDA stimulated cGMP production, which was inhibited by NG-nitro-l-arginine. Superoxide dismutase (100 U/mL) shifted the concentration-response relationship of MK801-mediated inhibition of NANC relaxation to the right (EC50 = 3.4 x 10–5 M), whereas catalase did not. Treatment with DETCA shifted the concentration-response relationships of pyrogallol-, ketamine- and MK801-mediated inhibition of NANC relaxation to the left. These findings suggest that the peripheral NMDA receptors mediate NANC smooth muscle relaxation, and modulate it, in part, through extracellular production of superoxide anions, thus eliminating the relaxant effect of endogenous nitric oxide.






Lippincott, Williams & Wilkins 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 HighWire Press
Copyright © 2005 by the International Anesthesia Research Society.