Effects of kappa opiate agonists on neurochemical and neuroendocrine indices: evidence for kappa receptor subtypes.
Four kappa opiate agonists, U-50488H, MR-2034, EKC and tifluadom, elevated plasma corticosterone and decreased plasma TSH in a dose-dependent manner. These effects were naloxone-reversible. However, WIN 44441-3, a long acting narcotic antagonist, was unable to reverse the effects of U-50488H and MR-2034 upto doses of 5 mg/kg. U-50488H and MR-2034 but not tifluadom or EKC, also increased levels of DOPAC and HVA in the olfactory tubercle. This effect was also naloxone-reversible but not WIN 44441-3 reversible. Tifluadom and EKC did not increase DOPAC and HVA. The differential responses of the tested kappa agonists to WIN 44441-3 antagonism and dopamine metabolism in A10 neurons suggest that the kappa agonists can be separated into two groups. This is the first physiological evidence suggestive of kappa opioid receptor subtypes.
D000818:Animals; D003345:Corticosterone / Q000097:blood*; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D009830:Olfactory Bulb / Q000378:metabolism*; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000145:classification / Q000494:pharmacology*; D017473:Receptors, Opioid, kappa; D013972:Thyrotropin / Q000097:blood*
D011957:Receptors, Opioid; D017473:Receptors, Opioid, kappa; D009270:Naloxone; D013972:Thyrotropin; D004298:Dopamine; D003345:Corticosterone