Desensitization and internalization of adenosine A1 receptors in rat brain by in vivo treatment with R-PIA: involvement of coated vesicles.
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, total number of adenosine A1 receptors and steady-state level of alpha-Gi in synaptic plasma membranes. An increase in the steady-state level of alpha-Gs in synaptic plasma membranes was also observed by R-PIA treatment. Concurrently, a significant increase of adenosine A1 receptors was observed in microsomes and coated vesicles. These results demonstrate adenosine A1 receptor desensitization in rat brain by 'in vivo' treatment with R-PIA and suggest a role for coated vesicles in the internalization of G-protein coupled receptors.
Ruiz
A
A
Area de Bioquímica, Facultad de C. Químicas, Universidad de Castilla-La Mancha, Ciudad Real, Spain.
Sanz
J M
JM
Gonzalez-Calero
G
G
Fernández
M
M
Andrés
A
A
Cubero
A
A
Ros
M
M
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000067956:Adenylyl Cyclase Inhibitors; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D018699:Coated Vesicles / Q000187:drug effects* / Q000378:metabolism; D005576:Colforsin / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D006160:Guanosine Triphosphate / Q000494:pharmacology; D015151:Immunoblotting; D007425:Intracellular Membranes / Q000378:metabolism; D008297:Male; D008861:Microsomes / Q000378:metabolism; D058906:Purinergic P1 Receptor Agonists; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D018047:Receptors, Purinergic P1 / Q000187:drug effects* / Q000378:metabolism; D014665:Vasodilator Agents / Q000494:pharmacology*; D014970:Xanthines / Q000494:pharmacology
D000067956:Adenylyl Cyclase Inhibitors; D058906:Purinergic P1 Receptor Agonists; D018047:Receptors, Purinergic P1; D014665:Vasodilator Agents; D014970:Xanthines; D005576:Colforsin; C047235:N-(1-methyl-2-phenylethyl)adenosine; C027513:N(6)-cyclohexyladenosine; D006160:Guanosine Triphosphate; C051360:1,3-dipropyl-8-cyclopentylxanthine; D000241:Adenosine