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A3Adenosine Receptorsin Human AstrocytomaCells:Agonist-MediatedDesensitization,Internalization, andDown-Regulation Maria Letizia TrincavelliDaniela TuscanoMatteo Marroni2002 год

A3Adenosine Receptors in Human Astrocytoma Cells: Agonist-Mediated Desensitization, Internalization, and Down-Regulation
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Аннотация: A3 adenosine receptor activation has been previously demonstrated to result in both neuroprotective and neurodegenerative effects, depending upon specific pathophysiological conditions. This dual effect may depend on receptor regulation mechanisms that are able to change receptor availability and/or function. In the present study, we investigated desensitization, internalization, and down-regulation of native A3 adenosine receptors in human astrocytoma cells after exposure to the agonist 2-chloro-N6-(3-iodobenzyl)-N-methyl-5′-carbamoyladenosine (Cl-IBMECA). Cl-IBMECA induced a concentration-dependent inhibition of adenylyl cyclase activity with an EC50 value of 2.9 ± 0.1 nM. The effect was suggested to be mediated by A3 adenosine receptor subtype by the use of selective adenosine receptor antagonists. Cell treatment with pertussis toxin abolished Cl-IBMECA-mediated inhibition of adenylyl cyclase activity, evidencing an A3 receptor coupling to inhibitory G protein. Short-term exposure to the agonist Cl-IBMECA (100 nM) caused rapid receptor desensitization, within 15 min. Agonist-induced desensitization was accompanied by receptor internalization: A3 adenosine receptor internalized with rapid kinetics, within 30 min, after cell exposure to 100 nM Cl-IBMECA. The localization of A3 adenosine receptors on the plasma membrane and in intracellular compartments was directly revealed by immunogold electron microscopy. After desensitization, the removal of agonist led to the restoration of A3 adenosine receptor functioning through receptor recycling to the cell surface within 120 min. Prolonged agonist exposure (1–24 h) resulted in a marked down-regulation of A3 adenosine receptors that reached 21.9 ± 2.88% of control value after 24 h. After down-regulation, the recovery of receptor functioning was slow (24 h) and associated with the restoration of receptor levels close to control values. In conclusion, our results demonstrated that A3receptors, in astrocytoma cells, are regulated after short- and long-term agonist exposure.
Год издания: 2002
Авторы: Maria Letizia Trincavelli, Daniela Tuscano, Matteo Marroni, Alessandra Falleni, Vittorio Gremigni, Stefania Ceruti, Maria P. Abbracchio, Kenneth A. Jacobson, F. Cattabeni, Claudia Martini
Издательство: American Society for Pharmacology and Experimental Therapeutics
Источник: Molecular Pharmacology
Ключевые слова: Adenosine and Purinergic Signaling, Receptor Mechanisms and Signaling, Pharmacological Receptor Mechanisms and Effects
Другие ссылки: Molecular Pharmacology (HTML)
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Europe PMC (PubMed Central) (HTML)
PubMed Central (HTML)
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