Spinal kappa1 and kappa2 opioid binding sites in rats, guinea pigs, monkeys and humans.
Several lines of work demonstrate that there are two subtypes of kappa opioid receptors. Intrathecally administered agonists for the kappa1 subtype are not effective in treating pain, whereas agonists for the kappa2 receptor are anti-hyperalgesic and anti-allodynic. The question addressed here was whether the ratio of spinal kappa1 to kappa2 receptors was conserved across species. Thus, binding experiments were performed on spinal cord membranes from rats, guinea pigs, monkeys and humans. We found that kappa2 receptors were approximately ten times more abundant than kappa1 receptors in all species tested. This suggests that the anti-hyperalgesic and anti-allodynic properties of kappa2 agonists may also be conserved. Therefore, selective kappa2 agonists may be effective in treating chronic pain in humans.
Pain and Neurosensory Mechanisms Branch, National Institute of Dental Research, National Institutes of Health, Bethesda, MD 20892, USA.
R M
RM
Caudle
A A
AA
Finegold
A J
AJ
Mannes
M D
MD
Tobias
D R
DR
Kenshalo
M J
MJ
Iadarola
D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D044482:Benzeneacetamides; D001575:Benzomorphans / Q000493:pharmacokinetics / Q000494:pharmacology; D006168:Guinea Pigs; D006801:Humans; D066298:In Vitro Techniques; D008252:Macaca fascicularis; D008253:Macaca mulatta; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D011759:Pyrrolidines / Q000493:pharmacokinetics / Q000494:pharmacology; D051381:Rats; D017473:Receptors, Opioid, kappa / Q000819:agonists / Q000378:metabolism*; D013045:Species Specificity; D013116:Spinal Cord / Q000033:anatomy & histology / Q000378:metabolism*
D000700:Analgesics; D044482:Benzeneacetamides; D001575:Benzomorphans; D011759:Pyrrolidines; D017473:Receptors, Opioid, kappa; C027248:bremazocine; C045444:U 69593