Adenosine receptor expression and function in rat striatal cholinergic interneurons

Cholinergic neurons were identified in rat striatal slices by their size, membrane properties, sensitivity to the NK 1 receptor agonist (Sar 9 , Met(O 2 ) 11 ) Substance P, and expression of choline acetyltransferase mRNA. A 1 receptor mRNA was detected in 60% of the neurons analysed, and A 2A receptor mRNA in 67% ( n =15). The A 1 receptor agonist R‐N 6 ‐(2‐phenylisopropyl)adenosine (R‐PIA) hyperpolarized cholinergic neurons in a concentration dependent manner sensitive to the A 1 antagonist 8‐cyclopentyl‐1,3‐dipropylxanthine (DPCPX, 100 n M ). In dual stimulus experiments, the A 2A receptor antagonist 8‐(3‐chlorostyryl)caffeine (CSC, 500 n M ) decreased release of [ 3 H]‐acetylcholine from striatal slices (S2/S1 0.78±0.07 versus 0.95±0.05 in control), as did adenosine deaminase (S2/S1 ratio 0.69±0.05), whereas the A 1 receptor antagonist DPCPX (100 n M ) had no effect (S2/S1 1.05±0.14). In the presence of adenosine deaminase the adenosine A 2A receptor agonist 2‐p‐((carboxyethyl)phenylethylamino)‐5′‐N‐ethylcarboxamidoadenosine (CGS21680, 10 n M ) increased release (S2/S1 ratio 1.03±0.05 versus 0.88±0.05 in control), an effect blocked by the antagonist CSC (500 n M , S2/S1 0.68±0.05, versus 0.73±0.08 with CSC alone). The combined superfusion of bicuculline (10 μ M ), saclofen (1 μ M ) and naloxone (10 μ M ) had no effect on the stimulation by CGS21680 (S2/S1 ratio 0.99±0.04). The A 1 receptor agonist R‐PIA (100 n M ) inhibited the release of [ 3 H]‐acetylcholine (S2/S1 ratio 0.70±0.03), an effect blocked by DPCPX (S2/S1 ratio 1.06±0.07). It is concluded that both A 1 and A 2A receptors are expressed on striatal cholinergic neurons where they are functionally active.British Journal of Pharmacology (2000) 130 , 886–890; doi: 10.1038/sj.bjp.0703366