Classification of adenosine receptors mediating antinociception in the rat spinal cord

Analogues of adenosine were injected intrathecally into rats implanted with chronic indwelling cannulae in order to determine a rank order of potency and hence characterize adenosine receptors involved in spinal antinociception. In the tail flick test L-N6-phenylisopropyl adenosine (L-PIA), cyclohexyladenosine (CHA) and 5'-N-ethylcarboxamide adenosine (NECA) produced dose-related antinociception which attained a plateau level. NECA and CHA also produced an additional distinct second phase of antinociception. D-N6-Phenylisopropyl adenosine (D-PIA) and 2-chloroadenosine (CADO) had very little antinociceptive activity in this test. The rank order of potency in producing the plateau effect was L-PIA greater than CHA greater than NECA greater than D-PIA = CADO, while that for the second phase of antinociception was NECA greater than-CHA. Pretreatment with both theophylline and 8-phenyltheophylline (8-PT) antagonized antinociception produced by CHA, with 8-PT being at least an order of magnitude more potent than theophylline. Both antagonists produced a significant hyperalgesia in the tail flick test. L-PIA and CHA also produced methylxanthine-sensitive antinociception in the hot plate test. These results suggest that activation of A1-receptors in the spinal cord can produce antinociception. Activation of A2-receptors may produce an additional effect, but the relative activity of CHA in this component of activity is unusual.LR: 20061115; PUBM: Print; JID: 7502536; 0 (Receptors, Cell Surface); 0 (Receptors, Purinergic); 146-77-0 (2-Chloroadenosine); 29193-86-0 (Phenylisopropyladenosine); 35920-39-9 (Adenosine-5'-(N-ethylcarboxamide)); 36396-99-3 (N(6)-cyclohexyladenosine); 58-55-9 (Theophylline); 58-61-7 (Adenosine); 961-45-5 (8-phenyltheophylline); ppublishSource type: Prin