Antinociceptive effects of intracerebroventricularly administered P2 purinoceptor agonists in the rat.
We examined the effects of adenosine 5'-triphosphate (ATP) and its analogues administered intracerebroventricularly on nociceptive thresholds in rats. Intracerebroventricular (i.c.v.) administration of ATP (10 and 100 nmol/rat), alpha,beta-methylene-ATP (1-30 nmol/rat) and 2', 3'-O-(4-benzoylbenzoyl)-ATP (1-30 nmol/rat) dose-dependently elevated the mechanical nociceptive threshold in the paw pressure test. These antinociceptive effects were rapid and short-lasting, peaking at 5 min and disappearing by 20 min after the administration. However, i.c.v. administration of beta,gamma-methylene-ATP (1-30 nmol/rat) and UTP (10 and 100 nmol/rat) had no significant effects on the mechanical nociceptive threshold. In other tests, i.c.v. administration of alpha,beta-methylene-ATP (10 and 30 nmol/rat) prolonged the thermal nociceptive latency in the hot plate test, but only a higher dose (30 nmol/rat) of alpha,beta-methylene-ATP prolonged the latency in the tail flick test. alpha,beta-Methylene-ATP produced no motor deficit in the inclined plane test. These results suggest that P2X purinoceptors play an inhibitory role in nociception at the supraspinal level.
Fukui
M
M
Department of Molecular Pharmacology, Faculty of Pharmaceutical Sciences, Kyoto University, 606-8501, Kyoto, Japan
Nakagawa
T
T
Minami
M
M
Satoh
M
M
D000255:Adenosine Triphosphate / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D018755:GABA Agonists / Q000494:pharmacology; D007276:Injections, Intraventricular; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects*; D058910:Purinergic P2 Receptor Agonists; D051381:Rats; D017207:Rats, Sprague-Dawley; D018048:Receptors, Purinergic P2 / Q000378:metabolism
D000700:Analgesics; D018755:GABA Agonists; D058910:Purinergic P2 Receptor Agonists; D018048:Receptors, Purinergic P2; C033901:3'-O-(4-benzoyl)benzoyladenosine 5'-triphosphate; D000255:Adenosine Triphosphate; D001418:Baclofen; C002630:alpha,beta-methyleneadenosine 5'-triphosphate