Location and Characteristics of Nitric Oxide Synthase in Sheep Spinal Cord and Its Interaction with α2-Adrenergic and Cholinergic Antinociception

Anesthesiology - Tập 84 Số 4 - Trang 890-899. - 1996
Zemin Xu1, Ping Li, Chuanyao Tong2, Jorge Figueroa3, Joseph R. Tobin4, James C. Eisenach5
1Perinatal Research Laboratories, Wake Forest University Medical Center, Winston-Salem, North Carolina, USA.
2Research Assistant Professor, Department of Anesthesia.
3Associate Professor, Departments of Obstetrics and Gynecology and Physiology and Pharmacology.
4Associate Professor, Department of Anesthesia.
5Professor and Chair for Anesthesia Research, Department of Anesthesia.

Tóm tắt

Background Nitric oxide synthase is located in the spinal cord dorsal horn and intermediolateral cell column, where it may modulate sensory and sympathetic neuronal activity. However, the biochemical characteristics of this enzyme have not been examined in these different areas in the spinal cord. Although alpha(2)-adrenergic agonists, muscarinic agonists, and nitric oxide may interact in the spinal cord to produce antinociception, these interactions have not been characterized. Methods Sheep spinal cord tissue was homogenized ad centrifuged at high sped to separate soluble and membrane-bound fractions. Nitric oxide synthase activity was determined by conversion of [(14)C]-L-arginine to [(14)C]-L-citrulline and its kinetic characteristics, dependency on cofactors, and sensitivity to inhibitors determined. Sheep spinal cord was stained for nicotinamide adenine dinucleotide phosphate diaphorase as a marker for nitric oxide synthase. Antinociception to a mechanical stimulus from intrathecal clonidine alone and with neostigmine was determined and the effects of L-arginine and n-methyl-L-arginine were determined. Results More than 85% of nitric oxide synthase activity was present in the soluble form and its kinetic, cofactor, and antagonist properties were similar to those of the neuronal isoform of nitric oxide synthase. Biochemical and histochemical studies localized nitric oxide synthase to the superficial dorsal horn and the intermediolateral cell column. Clonidine antinociception was enhanced by L-arginine and neostigmine, but not by D-arginine. Neostigmine's enhancement of clonidine antinociception was blocked by n-methyl-L-arginine. Conclusions These results confirm those of previous studies demonstrating localization of nitric oxide synthase to superficial dorsal horn and intermediolateral cell column of mammalian spinal cord, and suggesting its identity as the neuronal isoform. Spinal alpha(2)-adrenergic agonist antinociception may be partly dependent on cholinergic and nitric oxide mechanisms.

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Anesthesiology

Tập 84 Số 4

890-899.

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