The role of minoxidil on endogenous opioid peptides in the spinal cord: a putative co-agonist relationship between K-ATP openers and opioids.
ATP-gated K(+) channel openers produce antinociception that is attenuated by opioid receptor antagonists, indicating K-ATP openers produce antinociception, in part, via the release of endogenous opioid peptides. Utilizing the spinal perfusion method, male Sprague-Dawley rats were administered minoxidil intrathecally (i.t.) at doses ranging from 12.5 to 200 microg/rat for 3 min, tested for antinociception using the tail-flick test, and perfused with artificial cerebrospinal fluid (aCSF) to collect endogenous opioid peptides. Endogenous opioid peptide levels were measured by radioimmunoassay. Naltrindole, a delta-opioid receptor antagonist, at 4 mg/kg, subcutaneously (s.c.), blocked minoxidil-induced antinociception. beta-Funaltrexamine, a mu-opioid receptor antagonist, at 100 microg/rat, partially blocked minoxidil, whereas the kappa-opioid receptor antagonist nor-binaltorphimine, at a dose of 100 microg/rat, did not attenuate minoxidil. Although antagonists of the mu- and delta-opioid receptor attenuated minoxidil-induced antinociception, there was no increase in beta-endorphin, an endogenous ligand with affinity for both micro- and delta-opioid receptors or [Leu(5)]enkephalin, an endogenous ligand with affinity for delta-opioid receptors.
Campbell
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National Institute on Drug Abuse, 5500 Nathan Shock Drive Bldg. C, 21224, Baltimore, MD 21224, USA. vcampbel@intra.nida.nih.gov
Welch
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D000255:Adenosine Triphosphate / Q000502:physiology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D008297:Male; D008914:Minoxidil / Q000494:pharmacology*; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009619:Nociceptors / Q000187:drug effects; D018847:Opioid Peptides / Q000378:metabolism*; D010146:Pain / Q000517:prevention & control; D015221:Potassium Channels / Q000819:agonists; D051381:Rats; D017207:Rats, Sprague-Dawley; D011957:Receptors, Opioid / Q000819:agonists; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism; D014665:Vasodilator Agents / Q000494:pharmacology*
D009292:Narcotic Antagonists; D018847:Opioid Peptides; D015221:Potassium Channels; D011957:Receptors, Opioid; D014665:Vasodilator Agents; C051844:norbinaltorphimine; D008914:Minoxidil; D009271:Naltrexone; C024524:beta-funaltrexamine; D000255:Adenosine Triphosphate; C055382:naltrindole