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.
D015762:2-Chloroadenosine; D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D019830:Adenosine-5'-(N-ethylcarboxamide); D000818:Animals; D004305:Dose-Response Relationship, Drug; D008297:Male; D010146:Pain; D010660:Phenylisopropyladenosine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000145:classification* / Q000502:physiology; D011983:Receptors, Purinergic; D013116:Spinal Cord / Q000502:physiology*; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology
D011956:Receptors, Cell Surface; D011983:Receptors, Purinergic; D015762:2-Chloroadenosine; D010660:Phenylisopropyladenosine; D019830:Adenosine-5'-(N-ethylcarboxamide); C027513:N(6)-cyclohexyladenosine; D013806:Theophylline; C028322:8-phenyltheophylline; D000241:Adenosine