Synaptosomes from various rat brain areas show saturable and specific binding to an adenosine A(1) receptor ligand [Dagani et al. (1993): Drug Dev Res 28:359-363]. in this study, the functional correlates of these receptors were characterized in rat hippocampal synaptosomes by evaluating the ability of the adenosine analogue cyclo-pentyl-adenosine (CPA) to modulate KCl- and veratridine-induced glutamate outflow. CPA concentration-dependently reduced both depolarization-induced glutamate release and the associated increases of intrasynaptosomal Ca2+ concentrations. Maximal reduction by 100 mu M CPA (30% and 40% with respect to control for veratridine- and KCI-induced release, respectively) was completely antagonized by the xanthine adenosine receptor blocker bamyfilline, confirming the involvement of adenosine A(1) receptors. CPA selectively affected outflow of glutamate, with no significant influence on release of aspartate or GABA. Experiments performed in the absence of extrasynaptosomal Ca2+ ions suggested that adenosine selectively modulates glutamate Ca2+-dependent vesicular pool. Transductional studies showed that mobilization of Ca2+ from intrasynaptosomal inositol-phosphate-sensitive stores does not contribute to adenosine effects on release, therefore implying that CPA reduction of Ca2+ influx is due to direct effects on membrane Ca2+ conductance. Conversely, activation of A(1) receptors resulted in inhibition of forskolin-stimulated cAMP production in the same agonist concentration range effective on modulation of release, suggesting that this second messenger may play a role in the presynaptic effects of adenosine analogues. Finally, CPA reduced both glutamate efflux and the increases of internal Ca2+ concentrations associated with block of synaptosomal energy metabolism with rotenone and iodoacetic acid, suggesting that presynaptic A, receptors represent a strategic site of action for adenosine also under experimental conditions resembling brain ischemia and hypoxia. (C) 1995 Wiley-Liss, Inc.
ADENOSINE A(1) RECEPTORS IN RAT-BRAIN SYNAPTOSOMES - TRANSDUCTIONAL MECHANISMS, EFFECTS ON GLUTAMATE RELEASE, AND PRESERVATION AFTER METABOLIC INHIBITION / M. ABBRACCHIO, R. BRAMBILLA, M. CAMISA, G. ROVATI, R. FERRARI, L. CANEVARI, F. DAGANI, F. CATTABENI. - In: DRUG DEVELOPMENT RESEARCH. - ISSN 0272-4391. - 35:3(1995), pp. 119-129.
|Titolo:||ADENOSINE A(1) RECEPTORS IN RAT-BRAIN SYNAPTOSOMES - TRANSDUCTIONAL MECHANISMS, EFFECTS ON GLUTAMATE RELEASE, AND PRESERVATION AFTER METABOLIC INHIBITION|
ABBRACCHIO, MARIA PIA (Primo)
CATTABENI, FLAMINIO NICOLA (Ultimo)
|Settore Scientifico Disciplinare:||Settore BIO/14 - Farmacologia|
|Data di pubblicazione:||1995|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1002/ddr.430350302|
|Appare nelle tipologie:||01 - Articolo su periodico|