Peripheral N-methyl-D-aspartate receptors modulate nonadrenergic noncholinergic lower esophageal sphincter relaxation in rabbits

Atsushi Kohjitani, Makoto Funahashi, Takuya Miyawaki, Motohiko Hanazaki, Ryuji Matsuo, Masahiko Shimada

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

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)cyclo- hepten-5,10-imine) inhibited NANC relaxation in a concentration-dependent manner (EC50 = 1.5 × 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 × 10-5 M), whereas catalase did not. Treatment with DE-TCA 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.

Original languageEnglish
Pages (from-to)1681-1688
Number of pages8
JournalAnesthesia and Analgesia
Volume101
Issue number6
DOIs
Publication statusPublished - Dec 2005

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

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