Modulatory effects of probenecid on the nitroglycerin-induced changes in the rat caudal trigeminal nucleus

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Abstract

Four hours after systemic administration of the nitric oxide donor nitroglycerin (10 mg/kg bodyweight, s.c.), the neurons of the rat caudal trigeminal nucleus are activated, the area covered by calcitonin gene-related peptide (CGRP)-immunoreactive fibres is decreased and the neuronal nitric oxide synthase (nNOS)- and the calmodulin-dependent protein kinase II alpha (CamKIIα)-immunopositive neurons in the same area are increased. Probenecid is a non-selective inhibitor of multidrug-resistance associated proteins and organic anion transporters thus it can modulate the transport functions in the central nervous system influencing nociception. Accordingly, the aim of the present experiments was to examine the effects of probenecid administration on the nitroglycerin-induced expressions of nNOS, CamKIIα and CGRP in the rat caudal trigeminal nucleus. Probenecid (200 mg/kg bodyweight, i.p.) pretreatment proved to mitigate the nitroglycerin-induced changes in expression in the rat caudal trigeminal nucleus. The data suggest that the changes caused by nitroglycerin in the expressions of CGRP, nNOS and CamKIIα can be influenced by probenecid modulating the inflammatory functions in the nervous system. These data may be of relevance for the pathogenesis of migraine headache.

Original languageEnglish
Pages (from-to)33-37
Number of pages5
JournalEuropean Journal of Pharmacology
Volume621
Issue number1-3
DOIs
Publication statusPublished - Oct 25 2009

Keywords

  • Calcitonin gene-related peptide
  • Calmodulin-dependent protein kinase II alpha
  • Caudal spinal trigeminal nucleus
  • Neuronal nitric oxide synthase
  • Nitroglycerin
  • Probenecid

ASJC Scopus subject areas

  • Pharmacology

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