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- Title
Participation of the opioid receptor – nitric oxide – cGMP – K<sup>+</sup> channel pathway in the peripheral antinociceptive effect of nalbuphine and buprenorphine in rats.
- Authors
Ortiz, Mario I.; Cariño-Cortés, Raquel; Castañeda-Hernández, Gilberto
- Abstract
The aim of this study was to examine if the peripheral antinociceptive effects of the opioid agonist/antagonist nalbuphine and buprenorphine involve the sequential participation of nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) synthesis followed by K+ channel opening in the formalin test. Wistar rats (180–220 g) were injected in the dorsal surface of the right hind paw with formalin (1%). Rats received a subcutaneous (s.c.) injection into the dorsal surface of the paw of vehicles or increasing doses of nalbuphine (50–200 μg/paw) or buprenorphine (1–5 μg/paw) 20 min before formalin injection into the paw. Nalbuphine antinociception was reversed by the s.c. injection into the paw of the inhibitor of NO synthesis (NG-nitro-l-arginine methyl ester (L-NAME)), by the inhibitor of guanylyl cyclase (1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ)), by the Kir6.1–2, ATP-sensitive K+ channel inhibitors (glibenclamide and glipizide), by the KCa2.1–3, small conductance Ca2+-activated K+ channel blocker (apamin), by the KCa1.1, large conductance Ca2+-activated K+ channel blocker (charybdotoxin), and by the KV, voltage-dependent K+ channel inhibitors (4-aminopyridine (4-AP) and tetraethylammonium chloride (TEA)). The antinociceptive effect produced by buprenorphine was blocked by the s.c. injection of 4-AP and TEA but not by L-NAME, ODQ, glibenclamide, glipizide, apamin, or charybdotoxin. The present results provide evidence for differences in peripheral mechanisms of action between these opioid drugs.
- Subjects
POTASSIUM channels; CALCIUM-dependent potassium channels; OPIOID receptors; CYCLIC guanylic acid; NITRIC oxide; BUPRENORPHINE; GUANYLATE cyclase
- Publication
Canadian Journal of Physiology & Pharmacology, 2020, Vol 98, Issue 11, p753
- ISSN
0008-4212
- Publication type
Article
- DOI
10.1139/cjpp-2020-0104