Effects of aminoguanidine and meloxicam on nitric oxide and prostaglandin E production induced by lipopolysaccharide in the hypothalamus and anterior pituitary of the rat

Claudia Mohn, Alejandro Lomniczi, Alicia Faletti, Camila Scorticati, Juan C. Elverdin, Samuel M. Mccann, Valeria Rettori

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Background/Objective: Injection of bacterial lipopolysaccharide (LPS) into male rats activates genes that in turn induce many enzymes that participate in the animals' response to LPS. There is induction of inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2) in many tissues. This induction could result from combination with cell surface LPS receptors that directly induce both genes, or the nitric oxide (NO) released as a result of iNOS induction could induce COX-2. Methods: To distinguish between these two possibilities, specific inhibitors of iNOS and COX-2 activity, aminoguanidine (AG) and meloxicam (MLX), respectively, were injected either peripherally or intracerebroventricularly (i.c.v.), and their effect on NO and prostaglandin E (PGE) production induced by LPS in the medial basal hypothalamus (MBH) and anterior pituitary gland (AP) were determined. Results: Peripheral injection of AG blocked iNOS-derived NO production in the AP but not in the MBH. When AG was injected i.c.v., iNOS-derived NO production in the MBH was blocked. MLX injected peripherally blocked COX-2-derived PGE2 production in the MBH and AP, whereas AG injected peripherally or i.c.v. was ineffective. Since AG was only effective in blocking iNOS-derived NO production in the MBH when injected i.c.v., AG apparently does not effectively cross the blood brain barrier, whereas MLX injected peripherally inhibited PGE production, probably by inhibiting COX-2 activity in both the MBH and AP. AG was ineffective in preventing the increase in PGE derived from COX-2 in either the MBH or AP. Conclusion: LPS directly induces both enzymes, iNOS and COX-2, in the hypothalamus and AP.

Original languageEnglish (US)
Pages (from-to)276-285
Number of pages10
JournalNeuroImmunoModulation
Volume9
Issue number5
DOIs
StatePublished - 2001
Externally publishedYes

Fingerprint

meloxicam
Middle Hypothalamus
Anterior Hypothalamus
Nitric Oxide Synthase Type II
Cyclooxygenase 2
Anterior Pituitary Gland
Prostaglandins E
Lipopolysaccharides
Nitric Oxide
CD14 Antigens
Injections
Cell Surface Receptors
Enzymes
pimagedine
Blood-Brain Barrier
Dinoprostone
Genes
Hypothalamus

Keywords

  • Anterior pituitary
  • COX-2 inhibitor
  • Hypothalamus
  • iNOS inhibitor
  • Lipopolysaccharide

ASJC Scopus subject areas

  • Endocrinology
  • Neuroscience(all)
  • Immunology

Cite this

Effects of aminoguanidine and meloxicam on nitric oxide and prostaglandin E production induced by lipopolysaccharide in the hypothalamus and anterior pituitary of the rat. / Mohn, Claudia; Lomniczi, Alejandro; Faletti, Alicia; Scorticati, Camila; Elverdin, Juan C.; Mccann, Samuel M.; Rettori, Valeria.

In: NeuroImmunoModulation, Vol. 9, No. 5, 2001, p. 276-285.

Research output: Contribution to journalArticle

Mohn, Claudia ; Lomniczi, Alejandro ; Faletti, Alicia ; Scorticati, Camila ; Elverdin, Juan C. ; Mccann, Samuel M. ; Rettori, Valeria. / Effects of aminoguanidine and meloxicam on nitric oxide and prostaglandin E production induced by lipopolysaccharide in the hypothalamus and anterior pituitary of the rat. In: NeuroImmunoModulation. 2001 ; Vol. 9, No. 5. pp. 276-285.
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T1 - Effects of aminoguanidine and meloxicam on nitric oxide and prostaglandin E production induced by lipopolysaccharide in the hypothalamus and anterior pituitary of the rat

AU - Mohn, Claudia

AU - Lomniczi, Alejandro

AU - Faletti, Alicia

AU - Scorticati, Camila

AU - Elverdin, Juan C.

AU - Mccann, Samuel M.

AU - Rettori, Valeria

PY - 2001

Y1 - 2001

N2 - Background/Objective: Injection of bacterial lipopolysaccharide (LPS) into male rats activates genes that in turn induce many enzymes that participate in the animals' response to LPS. There is induction of inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2) in many tissues. This induction could result from combination with cell surface LPS receptors that directly induce both genes, or the nitric oxide (NO) released as a result of iNOS induction could induce COX-2. Methods: To distinguish between these two possibilities, specific inhibitors of iNOS and COX-2 activity, aminoguanidine (AG) and meloxicam (MLX), respectively, were injected either peripherally or intracerebroventricularly (i.c.v.), and their effect on NO and prostaglandin E (PGE) production induced by LPS in the medial basal hypothalamus (MBH) and anterior pituitary gland (AP) were determined. Results: Peripheral injection of AG blocked iNOS-derived NO production in the AP but not in the MBH. When AG was injected i.c.v., iNOS-derived NO production in the MBH was blocked. MLX injected peripherally blocked COX-2-derived PGE2 production in the MBH and AP, whereas AG injected peripherally or i.c.v. was ineffective. Since AG was only effective in blocking iNOS-derived NO production in the MBH when injected i.c.v., AG apparently does not effectively cross the blood brain barrier, whereas MLX injected peripherally inhibited PGE production, probably by inhibiting COX-2 activity in both the MBH and AP. AG was ineffective in preventing the increase in PGE derived from COX-2 in either the MBH or AP. Conclusion: LPS directly induces both enzymes, iNOS and COX-2, in the hypothalamus and AP.

AB - Background/Objective: Injection of bacterial lipopolysaccharide (LPS) into male rats activates genes that in turn induce many enzymes that participate in the animals' response to LPS. There is induction of inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2) in many tissues. This induction could result from combination with cell surface LPS receptors that directly induce both genes, or the nitric oxide (NO) released as a result of iNOS induction could induce COX-2. Methods: To distinguish between these two possibilities, specific inhibitors of iNOS and COX-2 activity, aminoguanidine (AG) and meloxicam (MLX), respectively, were injected either peripherally or intracerebroventricularly (i.c.v.), and their effect on NO and prostaglandin E (PGE) production induced by LPS in the medial basal hypothalamus (MBH) and anterior pituitary gland (AP) were determined. Results: Peripheral injection of AG blocked iNOS-derived NO production in the AP but not in the MBH. When AG was injected i.c.v., iNOS-derived NO production in the MBH was blocked. MLX injected peripherally blocked COX-2-derived PGE2 production in the MBH and AP, whereas AG injected peripherally or i.c.v. was ineffective. Since AG was only effective in blocking iNOS-derived NO production in the MBH when injected i.c.v., AG apparently does not effectively cross the blood brain barrier, whereas MLX injected peripherally inhibited PGE production, probably by inhibiting COX-2 activity in both the MBH and AP. AG was ineffective in preventing the increase in PGE derived from COX-2 in either the MBH or AP. Conclusion: LPS directly induces both enzymes, iNOS and COX-2, in the hypothalamus and AP.

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KW - COX-2 inhibitor

KW - Hypothalamus

KW - iNOS inhibitor

KW - Lipopolysaccharide

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