Brain and spinal cord kappa opiate receptors and pharmacological responses to U-50,488H in rats of differing ages.
The analgesic and hypothermic responses to U-50,488H (25 mg/kg IP), a kappa opiate receptor agonist, were determined in male Sprague-Dawley rats aged 4, 8, and 24 weeks. In addition, the characteristics of the binding of [3H]ethylketocylazocine (EKC) to kappa opiate receptors in whole brain and spinal cord of rats of three age groups were also determined. Administration of U-50,488H produced an age-related increase in the analgesic response in the rat, i.e., the older rats exhibited a higher intensity of analgesic response than the younger rats. U-50,488H also produced a hypothermic response. The response in 4- and 24-week-old rats was similar, but that in 8-week-old rats was smaller than the rats in the other two age groups. [3H]EKC bound to whole brain and spinal cord membranes of rats at a single high affinity site. The Bmax value of [3H]EKC in the brain and spinal cord of 24-week-old rats was significantly lower than in 4- and 8-week-old rats; however, the Kd values did not differ. It is concluded that kappa opiate receptor agonist produces age-related increase in its analgesic response and that such effects are not related to the characteristics of kappa receptors in the brain and spinal cord.
Department of Pharmacodynamics, University of Illinois at Chicago 60612.
H N
HN
Bhargava
G A
GA
Matwyshyn
P L
PL
Reddy
Veeranna
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000375:Aging / Q000502:physiology*; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D001923:Brain Chemistry / Q000187:drug effects*; D016314:Ethylketocyclazocine / Q000493:pharmacokinetics / Q000494:pharmacology; D008297:Male; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017473:Receptors, Opioid, kappa / Q000187:drug effects*; D013116:Spinal Cord / Q000187:drug effects* / Q000254:growth & development
D000700:Analgesics; D011759:Pyrrolidines; D017473:Receptors, Opioid, kappa; D016314:Ethylketocyclazocine; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer