Abstract

Nitric oxide (NO)-stimulated cGMP synthesis is present in the adult rat brain in close proximity to the NO-synthase containing structures [1]. Intracellular cGMP concentration is under very precise control and depends on parameters of its synthesis by guanylyl cyclase and degradation by phosphodiesterases (PDE). It is known that in the senescent brain the concentration of cGMP decreased [2]. When brain slices were incubated in the presence of isobutylmethylxanthine (IBMX), a nonselective phosphodiesterase inhibitor, sildenafil as a selective PDE5 inhibitor and BAY 60-7550 as a selective PDE2 inhibitor and DEANONOate as an NO donor, we have previously found that old brains are unresponsive to sildenafil treatment. Therefore in this study we wanted to investigate how the expression of cGMP selective phosphodiesterases changes in the brain during aging by using mRNA in situ hybridization.

Highlights

  • Nitric oxide (NO)-stimulated cGMP synthesis is present in the adult rat brain in close proximity to the NO-synthase containing structures [1]

  • Intracellular cGMP concentration is under very precise control and depends on parameters of its synthesis by guanylyl cyclase and degradation by phosphodiesterases (PDE)

  • When brain slices were incubated in the presence of isobutylmethylxanthine (IBMX), a nonselective phosphodiesterase inhibitor, sildenafil as a selective PDE5 inhibitor and BAY 60-7550 as a selective PDE2 inhibitor and DEANONOate as an NO donor, we have previously found that old brains are unresponsive to sildenafil treatment

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Summary

Introduction

Nitric oxide (NO)-stimulated cGMP synthesis is present in the adult rat brain in close proximity to the NO-synthase containing structures [1]. Address: 1Department of Psychiatry and Neuropsychology, Europewn Graduate School of Neuroscience (EURON), Maastricht University, Maastricht,6200 MD, The Netherlands.

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