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 mug/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 mug/rat, partially blocked minoxidil, whereas the kappa -opioid receptor antagonist nor-binaltorphimine, at a dose of 100 mug/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 mu- and delta -opioid receptors or [Leu(5)]enkephalin, an endogenous ligand with affinity for delta -opioid receptors. (C) 2001 Published by Elsevier Science B.V.