Kappa-opioid receptor mediated antinociception in rats is dependent on the functional state of dihydropyridine-sensitive calcium channels.
The modulatory effect of the dihydropyridine Ca2+ channel antagonist nimodipine on the analgesic action of the kappa-opioid receptor agonist U-69,593 was analyzed using the tail-flick test in rats. The antinociceptive effect of U-69,593 (0.25-4 mg/kg) was antagonized by L-type Ca2+ channel blockade with nimodipine (200 microgram/kg, i.p.), the ED50 being increased from 1.4 to 7.3 mg/kg. On the contrary, when an increase in the density of these channels was induced by means of chronic and simultaneous treatment with nimodipine (1 microgram/h, 7 days) and sufentanil (2 micrograms/h, 8 days), the analgesic effect of U-69,593 was potentiated by 5-fold. Our results suggest a functional coupling between kappa-opioid receptors and L-type Ca2+ channels in nociception.
Barro
M
M
Department of Physiology and Pharmacology, Faculty of Medicine, University of Cantabria, Santander, Spain.
Ruiz
F
F
Hurlé
M A
MA
D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D044482:Benzeneacetamides; D015220:Calcium Channels / Q000187:drug effects* / Q000502:physiology*; D004095:Dihydropyridines / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008297:Male; D009553:Nimodipine / Q000494:pharmacology; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology*; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017473:Receptors, Opioid, kappa / Q000502:physiology*; D017409:Sufentanil / Q000494:pharmacology
D000700:Analgesics; D044482:Benzeneacetamides; D015220:Calcium Channels; D004095:Dihydropyridines; D011759:Pyrrolidines; D017473:Receptors, Opioid, kappa; D009553:Nimodipine; D017409:Sufentanil; C045444:U 69593