PHARMACOLOGICAL COMPARISON OF THE SIGMA RECOGNITION SITE LABELED BY [3H]HALOPERIDOL IN HUMAN AND RAT CEREBELLUM

被引:17
作者
BARNES, JM
BARNES, NM
BARBER, PC
CHAMPANERIA, S
COSTALL, B
HORNSBY, CD
IRONSIDE, JW
NAYLOR, RJ
机构
[1] UNIV BIRMINGHAM,SCH MED,DEPT PHARMACOL,BIRMINGHAM B15 2TT,W MIDLANDS,ENGLAND
[2] UNIV BIRMINGHAM,SCH MED,DEPT PATHOL,BIRMINGHAM B15 2TT,W MIDLANDS,ENGLAND
[3] UNIV BRADFORD,SCH PHARM,POSTGRAD STUDIES PHARMACOL,BRADFORD BD7 1DP,W YORKSHIRE,ENGLAND
[4] WESTERN GEN HOSP,DEPT PATHOL,NEUROPATHOL LAB,EDINBURGH EH4 2XU,MIDLOTHIAN,SCOTLAND
关键词
SIGMA RECOGNITION SITES; HUMAN CEREBELLUM; RAT CEREBELLUM; 3H]HALOPERIDOL;
D O I
10.1007/BF00165736
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The radioligand binding characteristics of [H-3]haloperidol (in the presence of spiperone, 25 nmolL-1) were investigated in rat and human cerebellar membranes. In both rat and human cerebellar membrane preparations saturation studies with [H-3]haloperidol (non-specific binding defined by pentazocine, 10-mu-molL-1) demonstrated high affinity saturable specific binding to a homogenous population of binding sites (rat, Bmax 6693 +/- 1242 fmol mg-1 protein, pK(D) 8.33 +/- 0.08; human, Bmax 2550 +/- 437 fmol mg-1 protein, pK(D) 8.59 +/- 0.11; mean +/- SEM, n = 3-6). Competition studies employing a wide range of structurally diverse competing compounds displayed that the [H-3]haloperidol binding site was pharmacologically similar in both preparations and comparable to sigma recognition sites previously identified in various tissues originating from different species. In addition, with reference to the potential subtypes of sigma recognition sites, the labelling of these sites by low nanomolar concentrations of [H-3]haloperidol provides evidence that they belong to the sigma-1 recognition site subtype. The present findings suggest that the pharmacology of the rat and human cerebellar sigma recognition site are directly comparable and provides further supporting evidence towards the use of [H-3]haloperidol radioligand binding studies in the rat to detect sigma receptor ligands with potential therapeutic activity.
引用
收藏
页码:197 / 202
页数:6
相关论文
共 50 条
[1]   CHARACTERIZATION OF BINDING-SITES FOR [H-3] DTG, A SELECTIVE SIGMA-RECEPTOR LIGAND, IN THE SHEEP PINEAL-GLAND [J].
ABREU, P ;
SUGDEN, D .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1990, 171 (02) :875-881
[2]  
BOWEN WD, 1990, PROG CLIN BIOL RES, V328, P117
[3]  
BRADFORD MM, 1976, ANAL BIOCHEM, V72, P248, DOI 10.1016/0003-2697(76)90527-3
[5]  
CHENG Y, 1973, BIOCHEM PHARMACOL, V22, P3099
[6]   AN EARLY PHASE-II CLINICAL-TRIAL OF BW234U IN THE TREATMENT OF ACUTE SCHIZOPHRENIA IN NEWLY ADMITTED PATIENTS [J].
CHOUINARD, G ;
ANNABLE, L .
PSYCHOPHARMACOLOGY, 1984, 84 (02) :282-284
[7]  
CONNOR MA, 1990, FASEB J, V4, P330
[8]  
DAVIDSON J, 1982, Psychopharmacology Bulletin, V18, P173
[9]   CEREBRAL METABOLIC EFFECTS OF OMICRON-LIGANDS IN THE RAT [J].
DELLAPUPPA, A ;
LONDON, ED .
BRAIN RESEARCH, 1989, 505 (02) :283-290
[10]   BW234U, (CIS-9-[3-(3,5-DIMETHYL-1-PIPERAZINYL)PROPYL]CARBAZOLE DIHYDROCHLORIDE) - A NOVEL ANTIPSYCHOTIC AGENT [J].
FERRIS, RM ;
HARFENIST, M ;
MCKENZIE, GM ;
COOPER, B ;
SOROKO, FE ;
MAXWELL, RA .
JOURNAL OF PHARMACY AND PHARMACOLOGY, 1982, 34 (06) :388-390