Adenosine receptor expression and function in rat striatal cholinergic interneurons

1 Cholinergic neurons were Identified in rat striatal slices by their size, membrane properties, sensitivity to the NK1 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). 2 The A(1) receptor agonist R-N-o-(2-phenylisopropyl)adenosine (R-PIA) hyperpolarized cholinergic neurons rn a concentration dependent manner sensitive to the At antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, 100 nM). 3 In dual stimulus experimental the A(2A) receptor antagonist 8-(3-chlorostytyl)caffeine (CSC, 500 nM) decreased release of [H-3]-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 nM) had no effect (S2/S1 1.05+/-0.14). 4 In the presence of adenosine deaminase the adenosine A(2A) receptor agonist 2-p-((carboxyethyl)phenylethylamino) -5'-N-ethylcarboxamidoadenosine (CGS21680, 10 nM) increased release (S2/S1 ratio 1.03 +/- 0.05 Versus 0.88 +/- 0.05 in control), an effect blocked by the antagonist CSC (500 nM, S2/S1 0.68 +/- 0.05. versus 0.73 +/- 0.08 with CSC alone). The combined superfusion of bicuculline (10 mu M), saclofen (1 mu M) and naloxone (10 mu M) had no effect on the stimulation by CGS21680 (S2/S1 ratio 0.99 +/- 0.04). 5 The A(1) receptor agonist R-PIA (100 nM) inhibited the release of [H-3]-acetylcholine (S2/S1 ratio 0.70 +/- 0.03). an effect blocked by DPCPX (S2/S1 ratio 1.06 +/- 0.07). 6 It is concluded that both A(1) and A(2A) receptors are expressed on striatal cholinergic neurons where they are functionally active.