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Pharmacological and Functional Characterization of Adenosine A1 and A2A Receptors in Caudate Nucleus of Neonatal Lambs
Author(s) -
Ibe Basil,
McBride Shaemion,
Mier Mark,
Bernal Gilberto,
Guerra Catalina,
Rajaee Arezoo,
Koos Brian
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.933.2
Subject(s) - adenosine a2a receptor , cgs 21680 , adenosine , endocrinology , medicine , caudate nucleus , agonist , stimulation , signal transduction , chemistry , receptor , biology , microbiology and biotechnology , adenosine receptor
The basal ganglia including the caudate nucleus (CN) are critically involved in motor function with connections that include the sensorimotor sector of the thalamus. The CN, which has a high density of A2AR, has been implicated in the plasticity of the developing brain. We set out to identify intracellular signaling pathways in CN cells that are linked to A2AR activation that may be involved in neonatal brain plasticity. The hypothesis is that downstream effects of A2AR‐activation included modulation of cAMP/PKA signaling in CN cells. Culture of primary CN cells of neonatal lambs 4‐8d old were stimulated with different concentrations (uM, 10‐0.1) of CGS 21680 (CGS, A2AR agonist) compared to NECA. cAMP release and expression of A2AR, A1R, and PKA proteins were measured. Stimulation of cell proliferation by these agonists was also studied. CGS release of cAMP was dose‐dependent. A2AR antagonist SCH 58261(SCH) inhibited cAMP release. Also CGS increased while NECA decreased A2A receptor expression without affecting PKA expression. Both CGS and NECA stimulated caudate cell proliferation, PKA antagonist Rp‐cAMPS inhibited CGS stimulation of cell proliferation, A2AR, and PKA expression. These data show that cells from the caudate nucleus of neonatal lambs express functional A2AR and A1R that are linked to cAMP‐PKA signaling. These data may explain the greater plasticity of the neonatal brain attributed to the caudate nucleus. Supported by: Grant 20842: UCLA/LABiomed