title: [3H]dynorphin A binding and kappa selectivity of prodynorphin peptides in rat, guinea-pig and monkey brain.
abstract: We have previously demonstrated that [3H]dynorphin A selectively labels kappa opioid receptors in guinea-pig whole brain. In these current studies, using protection from inactivation by beta-chloronaltrexamine (beta-CNA), we are able to demonstrate that although dynorphin A prefers kappa receptors, it will label mu receptors when kappa receptors are not available, or present in only a small number. Thus, differences in numbers of mu and kappa receptors present in brain preparations are critical in determining the receptor binding profile of [3H]dynorphin A across species. Additionally, although all the prodynorphin derived peptides show kappa preference, the ability of the other prodynorphin derived peptides to compete with [3H]dynorphin A for its receptor varies across species. Consequently, in a highly enriched kappa preparation such as monkey cerebral cortex, [3H]dynorphin A appears to label kappa receptors with substantial selectivity, and the other prodynorphin-derived peptides show less ability to compete with dynorphin A for its receptor. In contrast, in a kappa-poor tissue such as rat brain, all of the prodynorphin-derived peptides, including dynorphin A-(1-8), show very similar potency. Thus, differences in mu and kappa receptor numbers across brain regions and species lead to differences in the receptor binding profile of dynorphin A.
authors.forename: E A
authors.initials: EA
authors.lastname: Young
authors.forename: J M
authors.initials: JM
authors.lastname: Walker
authors.forename: M E
authors.initials: ME
authors.lastname: Lewis
authors.forename: R A
authors.initials: RA
authors.lastname: Houghten
authors.forename: J H
authors.initials: JH
authors.lastname: Woods
authors.forename: H
authors.initials: H
authors.lastname: Akil
mesh_terms: D000477:Alkylating Agents / Q000494:pharmacology; D000818:Animals; D001575:Benzomorphans / Q000378:metabolism; D001923:Brain Chemistry / Q000187:drug effects*; D004399:Dynorphins / Q000378:metabolism*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008253:Macaca mulatta; D009020:Morphine / Q000378:metabolism; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D010455:Peptides / Q000378:metabolism*; D051381:Rats; D011957:Receptors, Opioid / Q000378:metabolism*; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D013237:Stereoisomerism
chemical_list: D000477:Alkylating Agents; D001575:Benzomorphans; D010455:Peptides; D011957:Receptors, Opioid; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; C032478:MR 2034; D009271:Naltrexone; C017120:chlornaltrexamine; D004399:Dynorphins; D009020:Morphine