Adenosine receptor expression and function in rat striatal cholinergic interneurons

Authors


Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QJ. E-mail: pjr1001@cam.ac.uk

Abstract

  • Cholinergic neurons were identified in rat striatal slices by their size, membrane properties, sensitivity to the NK1 receptor agonist (Sar9, Met(O2)11) Substance P, and expression of choline acetyltransferase mRNA. A1 receptor mRNA was detected in 60% of the neurons analysed, and A2A receptor mRNA in 67% (n=15).

  • The A1 receptor agonist R-N6-(2-phenylisopropyl)adenosine (R-PIA) hyperpolarized cholinergic neurons in a concentration dependent manner sensitive to the A1 antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, 100 nM).

  • In dual stimulus experiments, the A2A receptor antagonist 8-(3-chlorostyryl)caffeine (CSC, 500 nM) decreased release of [3H]-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 A1 receptor antagonist DPCPX (100 nM) had no effect (S2/S1 1.05±0.14).

  • In the presence of adenosine deaminase the adenosine A2A 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 μM), saclofen (1 μM) and naloxone (10 μM) had no effect on the stimulation by CGS21680 (S2/S1 ratio 0.99±0.04).

  • The A1 receptor agonist R-PIA (100 nM) inhibited the release of [3H]-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 A1 and A2A 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

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