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Modulation of cGMP accumulation by adenosine A1 receptors at the hippocampus: Influence of cGMP levels and gender
- Source :
- European Journal of Pharmacology
- Publication Year :
- 2014
- Publisher :
- Elsevier BV, 2014.
-
Abstract
- Adenosine A1 receptor is highly expressed in hippocampus where it inhibits neurotransmitter release and has neuroprotective activity. Similar actions are obtained by increasing cGMP concentration, but a clear link between adenosine A1 receptor and cGMP levels remains to be established. The present work aims to investigate if cGMP formation is modulated by adenosine A1 receptors at the hippocampus and if this effect is gender dependent. cGMP accumulation, induced by phosphodiesterases inhibitors Zaprinast (100 μM) and Bay 60-7550 (10 μM), and cAMP accumulation, induced by Forskolin (20 μM) and Rolipram (50 μM), were quantified in rat hippocampal slices using specific enzymatic immunoassays. N6-cyclopentyladenosine (CPA, 100 nM) alone failed to modify basal cGMP accumulation. However, the presence of adenosine deaminase (ADA, 2 U/ml) unmasked a CPA (0.03-300 nM) stimulatory effect on basal cGMP accumulation (EC50: 4.2±1.4 nM; Emax: 17±0.9%). ADA influence on CPA activity was specific for cGMP, since inhibition of cAMP accumulation by CPA was not affected by the presence of ADA, though ADA inhibited cAMP accumulation in the absence of CPA. Increasing cGMP accumulation, by about four-fold, with sodium nitroprusside (SNP, 100 μM) abolished the CPA (100 nM) effect on cGMP accumulation in males but did not modify the effect of CPA in female rats. This effect was reversed by 8-Cyclopentyl-1,3-dipropylxanthine (DPCPX, 100 nM), indicating an adenosine A1 receptor mediated effect on cGMP accumulation. In conclusion, adenosine A1 receptors increase intracellular cGMP formation at hippocampus both in males and females under basal conditions, but only in females when cGMP levels are increased by SNP.
- Subjects :
- Male
Nitroprusside
medicine.medical_specialty
Adenosine
Adenosine Deaminase
Phosphodiesterase 3
Biology
Hippocampus
chemistry.chemical_compound
Adenosine A1 receptor
Adenosine deaminase
Internal medicine
Cyclic AMP
medicine
Animals
Rats, Wistar
Cyclic GMP
Pharmacology
Forskolin
Receptor, Adenosine A1
Triazines
Colforsin
Imidazoles
Phosphodiesterase
Rats
Endocrinology
chemistry
Xanthines
biology.protein
Female
PDE10A
Zaprinast
Rolipram
medicine.drug
Subjects
Details
- ISSN :
- 00142999
- Volume :
- 744
- Database :
- OpenAIRE
- Journal :
- European Journal of Pharmacology
- Accession number :
- edsair.doi.dedup.....2f12fd21acd91edc925b8f800a64fefc