1996
DOI: 10.1016/0167-4889(95)00152-2
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Desensitization and internalization of adenosine A1 receptors in rat brain by in vivo treatment with R-PIA: involvement of coated vesicles

Abstract: Chronic treatment of rats with R-PIA 'in vivo' desensitized adenosine A1 receptor-mediated inhibition of adenylyl cyclase in brain plasma membranes and increased basal and forskolin-stimulated adenylyl cyclase. The adenosine A1 receptor agonist CHA (cyclohexyl adenosine) inhibited forskolin-stimulated adenylyl cyclase in synaptic plasma membranes from control rats but failed to do so in membranes isolated from rats treated with R-PIA. This loss of response was accompanied with a significant decrease in both, t… Show more

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Cited by 48 publications
(32 citation statements)
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“…This has been verified with A 1 receptors, which are down-regulated and desensitized after adenosine or analogue exposure in in vitro (Abbracchio et al 1992;Hettinger et al 1998;Vendite et al 1998) and in vivo systems Ruiz et al 1996). In agreement, acute activation of A 1 receptors is neuroprotective, reducing damage to neurons, whereas A 1 receptor blockade potentiates damage (Fredholm 1997;von Lubitz 1999;de Mendonça et al 2000).…”
supporting
confidence: 51%
“…This has been verified with A 1 receptors, which are down-regulated and desensitized after adenosine or analogue exposure in in vitro (Abbracchio et al 1992;Hettinger et al 1998;Vendite et al 1998) and in vivo systems Ruiz et al 1996). In agreement, acute activation of A 1 receptors is neuroprotective, reducing damage to neurons, whereas A 1 receptor blockade potentiates damage (Fredholm 1997;von Lubitz 1999;de Mendonça et al 2000).…”
supporting
confidence: 51%
“…Accordingly, upregulation of adenosine A 1 receptor expression has been observed in mice and rats after chemically induced seizures and in post-mortem tissue of humans suffering from epilepsy Vanore et al, 2001;Angelatou et al, 1991). An upregulation of adenosine A 1 receptors in the presence of extracellular adenosine at high concentrations (as it occurs during seizures) seems a rather unusual feature, since adenosine A 1 receptors are normally desensitized in the presence of high concentrations of adenosine or after a prolonged exposure to selective agonists (Abbracchio et al, 1992;Ruiz et al, 1996;Hettinger et al, 1998;Latini and Pedata, 2001). The data presented here might provide an explanation for this paradoxical situation, since IL-6-induced synthesis of A 1 receptors could counteract or overrule A 1 receptor desensitization caused by prolonged exposure to high levels of adenosine released during seizures.…”
Section: Discussionmentioning
confidence: 99%
“…In fact, several works suggest that neuronal A 1 R desensitization occurs in large time frames (12Y24 h) of exposure to exogenously added A 1 R agonists in vitro (e.g., [184,186,187]) as well as in vivo (e.g., [188,189]). The time course of desensitization of A 1 Rs is particularly critical to understand if adenosine maintains its neuroprotective efficiency in chronic noxious brain situations.…”
Section: Modification Of Adenosine Metabolism On Stressful Conditionsmentioning
confidence: 99%