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.
Bhargava
H N
HN
Department of Pharmacodynamics, University of Illinois at Chicago 60612.
Matwyshyn
G A
GA
Reddy
P L
PL
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