@article{9ac5ae9f31eb4d53b192f1bc849ecacd,
title = "Binding characteristics of kappa opioids in rat brain. A comparison of in vitro binding paradigms",
abstract = "Putative kappa binding was investigated in homogenates of the brain of the rat using [3H]ethylketocylazocine and [3H]diprenorphine under conditions where mu and delta sites were blocked. Under blocked conditions, the binding of [3H]ethylketocyclazocine labelled a single site, as defined by kinetic and equilibrium analysis, which showed high affinity for dynorphin 1-17, U50,488H, and benzomorphan compounds. However, blocked binding of [3H]diprenorphine showed a biphasic dissociation curve, and did not show high affinity for the specific kappa agonists dynorphin 1-17 or U50.488H. It is proposed that blocked [3H]ethylketocyclazocine is the more appropriate paradigm to study putative kappa binding, while blocked [3H]diprenorphine may label additional non-mu/non-delta sites.",
keywords = "binding paradigm, ethylketocyclazocine, kappa receptor, opiate receptor",
author = "Weyhenmeyer, {J. A.} and Mack, {K. J.}",
note = "Funding Information: Bowen, Herkenham and Pert, 1982) are kappa- (1979M) ultiple opiater eceptorsD: ifferentr egionald istri-agonists.F urther Lahti et al. (1982), using biochem-butioni n theb rainand differentiabl indingo f opiatesa nd ical and pharmacologicapl reparationsh ave shown opioid peptides.1 clolecP. harmac. 16: 91-104. that U50,488Hi s a highly specifick appa agonist.I t opiate binding sites selectivef or benzomorphand rugs. Chang K. J., Hazum E. and CautrecasaPs . (1981)N ovel seemsr easonablet hen to identify a site which has a Proc. natn. Acad. Sci. U.S.A. 78: 4141-4145. selectivelyh igh affinity for all of these ligands as ChengY . C. andP rusoffW . H. (1973R) elationshipb etween a kappa binding site. This condition is met by the inhibition constant( K,) and the concentrationo f the blocked [3H]ethylketocyclazocinbuet not by the zymaticr eaction.B iochem. Pharmac. 22: 3099-3 108. inhibitor which causes5 00/,i nhibition (I,,) of an en- blocked binding of [3H]diprenorphine. CzlonkowskiA .. CostaT .. PrzewlockiR ., Pasi A. and Herz To summarize,t he presentd ata has shown agree- A. (1983)O piater eceptorb inding sitesi n humans pinal ment betweent he basic kinetic and equilibrium par-cord. E&t Res. 267:-392-396._ ametersfo r blockedb inding of [3H]ethyiket~yclazo-Gillan M. G. C. and Kosterlitz H. W. (1982S) nectrumof tine. In addition, the findings are consistentw ith the Br. J. Phar~c. 77: 461-469. thep , 6-, and K-bindings itesi n homogenateosf rat brain. existenceo f a singlec lasso f high affinity sitesw hich Hiller J. M. and SimonE . J. (1979[)3 H]Ethylketocyclaz~ine are selectivefo r ligandsw ith known kappab iochem- binding:l ack of evidencefo r a separateK receptorin rat ical and pharmacologicalc haracteristicsA. lthough CNS. Eur. J. Pharmac. 60: 389-390. the prototypics igmal igand SKF 10,047c ross-reacts [3H]ethylketocyclazocibnien ding in rat central nervous Hiller J. M. and Simon E. J. (1980)S pecific,h igh affinity with this site,t he data clearly demonstrateth at SKF systemla ck of evidencefo r K receptorsJ.. Pharmac. exp. 10,047h ad almost no selectivityb etweent he opiate Ther. 214: 516-519. receptor subtypes shown in Table 3. However, Koltz I. M. (1982)N umberso f receptors ites from Scat- blocked binding of [3H]ethylketocyclazocinme ay chardg raphs:f actsa ndf antasiesS. cience2 17:1 247-1249. representb inding to more than one site. This is Propertieso f a selectivek appaa gonist,U SO-488H.L ife Lahti R. A., VonVoightlanderP . F. and Bars&n C. (1982) demonstratedb y the low Hill coefficientso bserved Sci. 31: 2257-2260. with the kappa agonistsd ynorphin and U50,488H Lord J. A. H., WaterlieldA . A., HughesJ . and Kosterlitz againstb locked binding of [3H]ethylketocycl~o~ne. H. W. (19771E ndoaenouso nioid oentides:M ultivle Further, the blocked binding of ~3HJdipreno~hine Mack K. J., Killian A. and WeyhenmeyeJr. A. (1984) agonistsa nd receptorsN. ature*267: 4%499. _ identified sites with a high affinity for the benzo-Comparisono f mu, delta,a nd kappao piateb indings ites morphans( ethylketocyclazocineb,r emazocineS, KF in rat brain and spinal cord. Life Sci. 34: 281-285, 10,047),a s was originally reported by Chang and Oka T. and NegishiK . (1982)E videncet hate ndogenouGs Cuatrecasas(1 981)a nd may indicate both a kappa receptorsa s agonists.L ife Sci. 81: 1707-1710. (Arg or Lys)-opioid peptides can interact with K- and an additional opiate binding site. Pfeiffer, Pasi, Oka T., NegishiK ., SudaM ., MatsumiyaT ., Inazu T. and Mehraeina nd Herz (1981)h aver eporteds imilar data Ueki M. (1980)R abbit vas deferensa: suecificb ioassav for blocked [{\textquoteleft}Hldiprenorphine,w hich showedh igh for opioid K-receptor agonists.E ur. J: Pharmac. 75: affinity for benzomorphansa nd biphasic inhibition 235-236. curvesf or dynorphin 1-17.F urther work is neededt o subclassificationo f K-sites in human brain by use of Pfeiffer A., Pasi A., Mehraein D. and Herz A. (1981)A substantiateth ee xactc haractero f blockedb inding of dynorphin l-17. Nearropepiides 2: 89-97. [3H]diprenorphine. Quirion R., Bowen W. P., HerkenhamM . and Pert C. B. (1982V) isuali~tiona nd ~IubiIi~tion of rat brain opiate receptorsw ith a “K” ligand selectivityp attern. Ceil. Acknowledgements-The authorswishto expresstheirgrat- Molec. Neuro~iol. 2: 333-346. itudetoDr A. Killian for his technicaaldvice,MSM. F. Lee Weiland G. A. and Molinoff P. B. (1981)Q uantitative for her technicalassistanceand to Mrs M. Gillett for the analysiso f drug-receptorin teractionsI:. Determination preparationofthis manuscriptT.hiswork was supportedin of kinetic and equilibrium properties. Life Sci. 29: part by NHLBI grant HL27757toJ.A.W. K.J.M. is sup-313-330.",
year = "1985",
month = feb,
doi = "10.1016/0028-3908(85)90169-8",
language = "English (US)",
volume = "24",
pages = "111--115",
journal = "Neuropharmacology",
issn = "0028-3908",
publisher = "Elsevier Limited",
number = "2",
}