PLATELET SEROTONIN STUDIES IN HYPERSEROTONEMIC RELATIVES OF CHILDREN WITH AUTISTIC DISORDER

被引:135
作者
COOK, EH
ARORA, RC
ANDERSON, GM
BERRYKRAVIS, EM
YAN, SY
YEOH, HC
SKLENA, PJ
CHARAK, DA
LEVENTHAL, BL
机构
[1] LOYOLA UNIV,STRITCH SCH MED,DEPT PHARMACOL,MAYWOOD,IL 60141
[2] YALE CHILD STUDY CTR,NEW HAVEN,CT 06510
[3] RUSH PRESBYTERIAN ST LUKES MED CTR,CHICAGO,IL 60612
[4] LOYOLA UNIV,STRITCH SCH MED,DEPT PSYCHIAT,MAYWOOD,IL 60141
[5] VET ADM MED CTR,HINES,IL 60141
关键词
D O I
10.1016/0024-3205(93)90685-V
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Platelet serotonin (5-HT) studies were conducted with 12 hyperserotonemic and 12 normoserotonemic age-, sex-, and relationship-matched relatives of autistic probands. Each group consisted of 7 mothers, 4 fathers, and 1 sister of autistic children and adolescents. The density (B(max)) of platelet 5-HT2 receptor binding sites, labelled with [H-3]-lysergic acid diethylamide (LSD), was significantly lower in 11 hyperserotonemic subjects compared to 12 normoserotonemic subjects (40.9 +/-13.5 fmol/mg protein, 59,6 +/- 13.2; p < 0.004). The affinity (K(d)) for [H-3]-LSD binding did not differ. Although the density (B(max)) of [H-3]-paroxetine binding did not differ between groups, there was a small difference in the affinity (K(d)) of [H-3]-paroxetine binding (hyperserotonemic 47.6 +/- 9.0 pM, normoserotonemic 54.8 +/-12.1; p < 0.05). There were no significant differences in platelet 5-HT uptake, or in thrombin-stimulated 5-HT release. Basal, 5-HT-stimulated, and arginine-vasopressin (AVP)-stimulated inositol phosphate production, as well as basal, prostaglandin E1 (PGE1)-, and forskolin-stimulated cAMP production did not differ. There were signficant correlations between whole blood 5-HT levels and LSD B(max) (r(S) = -0.63, N=23, p < 0.002) and whole blood 5-HT levels and 5-HT uptake V(max) (r(S) = 0.56, N=18, p < 0.02). However, [H-3]-LSD labelled 5-HT2 binding and 5-HT uptake were not correlated with each other. Hyperserotonemia of autism may be heterogeneous with one subgroup of subjects with increased 5-HT uptake and another subgroup with decreased 5-HT2 binding.
引用
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页码:2005 / 2015
页数:11
相关论文
共 36 条
  • [1] ELEVATED BLOOD SEROTONIN IN AUTISTIC PROBANDS AND THEIR 1ST-DEGREE RELATIVES
    ABRAMSON, RK
    WRIGHT, HH
    CARPENTER, R
    BRENNAN, W
    LUMPUY, O
    COLE, E
    YOUNG, SR
    [J]. JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS, 1989, 19 (03) : 397 - 407
  • [2] DETERMINATION OF SEROTONIN IN WHOLE-BLOOD, PLATELET-RICH PLASMA, PLATELET-POOR PLASMA AND PLASMA ULTRAFILTRATE
    ANDERSON, GM
    FEIBEL, FC
    COHEN, DJ
    [J]. LIFE SCIENCES, 1987, 40 (11) : 1063 - 1070
  • [3] PLATELET DENSE GRANULE RELEASE REACTION MONITORED BY HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY FLUOROMETRIC-DETERMINATION OF ENDOGENOUS SEROTONIN
    ANDERSON, GM
    HALL, LM
    YANG, JX
    COHEN, DJ
    [J]. ANALYTICAL BIOCHEMISTRY, 1992, 206 (01) : 64 - 67
  • [4] ACTIVATORS OF PROTEIN-KINASE-C DECREASE SEROTONIN TRANSPORT IN HUMAN PLATELETS
    ANDERSON, GM
    HORNE, WC
    [J]. BIOCHIMICA ET BIOPHYSICA ACTA, 1992, 1137 (03) : 331 - 337
  • [5] ANDERSON GM, 1981, CLIN CHEM, V27, P775
  • [6] WHOLE-BLOOD SEROTONIN IN AUTISTIC AND NORMAL SUBJECTS
    ANDERSON, GM
    FREEDMAN, DX
    COHEN, DJ
    VOLKMAR, FR
    HODER, EL
    MCPHEDRAN, P
    MINDERAA, RB
    HANSEN, CR
    YOUNG, JG
    [J]. JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY AND ALLIED DISCIPLINES, 1987, 28 (06): : 885 - 900
  • [7] A MODIFIED ASSAY-METHOD FOR DETERMINING SEROTONIN UPTAKE IN HUMAN-PLATELETS
    ARORA, RC
    MELTZER, HY
    [J]. CLINICA CHIMICA ACTA, 1981, 112 (02) : 225 - 233
  • [8] Baenziger N L, 1974, Methods Enzymol, V31, P149
  • [9] LITHIUM AMPLIFIES AGONIST-DEPENDENT PHOSPHATIDYLINOSITOL RESPONSES IN BRAIN AND SALIVARY-GLANDS
    BERRIDGE, MJ
    DOWNES, CP
    HANLEY, MR
    [J]. BIOCHEMICAL JOURNAL, 1982, 206 (03) : 587 - 595
  • [10] CYCLIC-AMP METABOLISM IN FRAGILE-X SYNDROME
    BERRYKRAVIS, E
    HUTTENLOCHER, PR
    [J]. ANNALS OF NEUROLOGY, 1992, 31 (01) : 22 - 26