Adenosine A1 receptor agonist treatment up-regulates rat brain metabotropic glutamate receptors.
Chronic R-N(6)-phenylisopropiladenosine (R-PIA) subcutaneous injection for 6 days significantly increased total glutamate receptor number (180% of control) in rat brain synaptic plasma membranes (SPM), without affecting receptor affinity. A higher increase in metabotropic glutamate (mGlu) receptor number (258% of control) was also detected, indicating that mGlu is the main type of glutamate receptor affected by this treatment. On the other hand, the observed increase in basal and calcium- and Gpp(NH)p-stimulated phospholipase C (PLC) activity after treatment was associated with a significant increase in PLC beta(1) isoform, detected in SPM by immunoblotting assays. Moreover, an increase in PLC activity stimulation with trans-ACPD, in the absence and in the presence of Gpp(NH)p, was detected after R-PIA treatment. These results show that mGlu receptors and its effector system, PLC activity, are up-regulated by chronic exposure to an adenosine A(1) receptor agonist and suggest the existence of a cross-talk mechanism between both signal transduction pathways in rat brain.
Albasanz
J L
JL
Area de Bioquímica, Departamento de Química Inorgánica, Orgánica y Bioquímica, Facultad de Ciencias Químicas, Centro Regional de Investigaciones Biomédicas, Universidad de Castilla-La Mancha, Avenida Camilo José Cela 10, 13071, Ciudad Real, Spain.
León
D
D
Ruíz
M A
MA
Fernández
M
M
Martín
M
M
D000241:Adenosine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000187:drug effects; D008297:Male; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology; D058906:Purinergic P1 Receptor Agonists; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000187:drug effects / Q000378:metabolism*; D018047:Receptors, Purinergic P1 / Q000187:drug effects; D015398:Signal Transduction / Q000502:physiology*; D010738:Type C Phospholipases / Q000187:drug effects; D015854:Up-Regulation / Q000502:physiology*
D018696:Neuroprotective Agents; D058906:Purinergic P1 Receptor Agonists; D018094:Receptors, Metabotropic Glutamate; D018047:Receptors, Purinergic P1; C047235:N-(1-methyl-2-phenylethyl)adenosine; D010738:Type C Phospholipases; D000241:Adenosine