nd Neutrochemca? Pyess, I In cpiate Alcehe/ 6f 6~X MecLanumJ 1e ~( ka we Aca datc pve fJ [ I<. Dlum ence 7L Peud, 79 446+649+55 H K1679155 THE OPIATE RECEPTOR* ROLE OF  PHOSPHATIDYL SERINE Salem, and N. Takeda, Abood, Brain Research Center for and of Biochemistry Department Medical Center of Rochester University York 14642 Rochester New INTRODUCTION receptor is configuration of the opiate and nolecular nature The nunber of laboratories intensive investigation problen under finding result the prob Lem developed interest responsible Our from brain may proteolipid fraction (4) that thers preparations various observed in stereospecific binding opiate proteins for proteolipids and various Iipids, examining Upon phosphatidyl brain tissue serine that found Vas fron membranes derived from brain exhibited stereospecific opiate major acidic lipid In brain_ (PS) the the opiate- and the opiate-PS ccudecxitnwas Ka" for Since the recognized binding (5) magnitude orders complex differed by chree from the high af- cissue and different to PS was nonspecific the binding that the V2s interested What nembrane preparations binding menbranous protein, finity complex with form of Possibility that PS the receptor the opiate important component of the may undertaken study Vas test this hypothesis effort In an for It had been known opiate binding: effect of added phospholipids capable of exchanging with endoz- vere that exogenous lipids years functional their natural many apparent alteration vith enous ones addition demonstrated that Ehe structural characteristics (6) _ Yas Snantic EcebranesvitrouE Captd enhanced both x 1079 euspensLons of PS 1.0 veing Kqa Nigdoyt8 *Pio lower affinity binding, the respectively high and x 10 and lipid being 5 those vith H and inhibi- thdesexobenousufes PE Vas of interest was Another observation (7) . tepoenhdecerebes and aimed Ptesent The opiate binding- tory attempt the PS-enhancenent findings the initial extending binding phospholipids In opiate role of PS and other understand the D4]00464_ USPH RThis research was supported grant phosphatidyl serine abbreviations used: are fThe folloving Phospha- lebosghafidyceethanoletiyfa Roniup ethanolanine phosphatidyl choline, oto phosphoinositides CTAB tidic acid, PI fluorosur- cationic "Zonyl cetylpyridiniumn chloride_ FSC dinitrodifluoro- nide CPC sodium dodecylsulfate, DNDEB (DuPont) SDS factant 3H-dfhydromorphine 3H-DHM benzene CTR MN CONFIDENTIAL MINNESOTA TOBaCCO LITIGATION
I Neutrochemca? nd In Pyess, MecLanumJ 6f Alcehe/ 6~X cpiate 1e ka we ~( I<. Dlum Aca datc pve fJ [ Peud, ence 79 7L 446+649+55 SERINE THE OPIATE RECEPTOR* H K1679155 ROLE OF  PHOSPHATIDYL Abood, Takeda, and N. Salem, Center for Brain Research and Department of Biochemistry University of Rochester Medical Center Rochester New York 14642 INTRODUCTION configuration of the opiate receptor is The nolecular nature and nunber of laboratories problen under intensive investigation result finding Our interest the prob Lem developed from brain may responsible thers (4) that proteolipid fraction observed in various preparations for stereospecific opiate binding proteolipids and proteins tissue Upon examining various Iipids, brain found that phosphatidyl serine fron membranes derived from brain Vas exhibited stereospecific opiate (PS) the major acidic lipid In brain_ the opiate-PS and the opiate- binding (5) Since the Ka" for ccudecxitnwas orders magnitude recognized cissue complex differed by chree and different from the high af- that the binding to PS was nonspecific What interested V2s the finity binding nembrane preparations complex with menbranous protein, Possibility that PS the form of important component of the opiate receptor may study Vas undertaken the In an effort test this hypothesis It had been known for effect of added phospholipids opiate binding: capable of exchanging with endoz- that exogenous lipids vere many years their natural functional enous ones vith apparent alteration demonstrated that Ehe addition structural characteristics (6) _ Yas enhanced both of PS euspensLons Snantic EcebranesvitrouE Captd 1.0 x 1079 lower affinity binding, the Kqa Nigdoyt8 *Pio veing high and x 10 and respectively H and those vith lipid being 5 PE Vas inhibi- (7) . Another observation of interest was thdesexobenousufes aimed opiate binding- The Ptesent tory tepoenhdecerebes and the PS-enhancenent attempt extending the initial findings phospholipids In opiate binding understand the role of PS and other USPH grant D4]00464_ RThis research was supported are used: phosphatidyl serine fThe folloving abbreviations ethanolanine Phospha- phosphatidyl choline, lebosghafidyceethanoletiyfa Roniup oto tidic acid, PI phosphoinositides CTAB FSC cationic "Zonyl fluorosur- nide CPC cetylpyridiniumn chloride_ sodium dodecylsulfate, DNDEB dinitrodifluoro- factant (DuPont) SDS benzene 3H-DHM 3H-dfhydromorphine CTR MN CONFIDENTIAL MINNESOTA TOBaCCO LITIGATION