ACTIVATORS OF PROTEIN-KINASE-C DECREASE SEROTONIN TRANSPORT IN HUMAN PLATELETS

被引:94
作者
ANDERSON, GM
HORNE, WC
机构
[1] YALE UNIV, SCH MED, DEPT LAB MED, NEW HAVEN, CT 06510 USA
[2] YALE UNIV, SCH MED, DEPT CELL BIOL, NEW HAVEN, CT 06510 USA
关键词
PROTEIN KINASE-C ACTIVATOR; SEROTONIN; MEMBRANE TRANSPORT; (HUMAN PLATELET);
D O I
10.1016/0167-4889(92)90154-4
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Treatment of human platelets with activators of protein kinase C (PKC) for 5-20 min resulted in substantial reductions in the rate of platelet serotonin (5-HT) transport. The mean V(max) observed after 5 min treatment with 1 muM 4-beta-12-tetradecanoylphorbol 13-acetate (beta-TPA) was 66% (n = 16, P = 0.0001) of the control value. 5 min of treatment with 1 muM mezerein reduced uptake to 78% (n = 3, P = 0.01) of control. Both beta-TPA and mezerein had little effect on the K(m) of transport and had EC50 values of approx. 100 nM when a 20-min treatment period was used. The maximum effects of both were reached at approx. 20 min and could be blocked with staurospine. The beta-TPA effect was stereospecific, as alpha-TPA did not alter platelet 5-HT uptake. Although the PKC activators may have altered transmembrane ion-gradients for Na+ and Cl-, which are co-transported with 5-HT, minimizing ion-gradient changes had little effect on the observed reductions in transport. The PKC activators also had little or no effect on platelet 5-HT release or on the number (B(max)) of 5-HT transporters expressed at the platelet surface. The data indicate that PKC activation may down-regulate the activity of the 5-HT transporter in platelets. Apparently, most of this effect is mediated through mechanisms other than changes in ion-gradients, reductions in the number of available transporters, or increased 5-HT release. The apparent regulation of 5-HT transport by PKC may have important implications in platelet and neuronal functioning.
引用
收藏
页码:331 / 337
页数:7
相关论文
共 54 条
[21]   MECHANISMS OF REGULATION OF THE NA+/H+ EXCHANGER [J].
GRINSTEIN, S ;
ROTHSTEIN, A .
JOURNAL OF MEMBRANE BIOLOGY, 1986, 90 (01) :1-12
[22]   REGULATION OF GLUTAMATE AND GABA TRANSPORT BY ADRENOCEPTORS IN PRIMARY ASTROGLIAL CELL-CULTURES [J].
HANSSON, E ;
RONNBACK, L .
LIFE SCIENCES, 1989, 44 (01) :27-34
[23]   CLONING OF A SEROTONIN TRANSPORTER AFFECTED BY ANTIDEPRESSANTS [J].
HOFFMAN, BJ ;
MEZEY, E ;
BROWNSTEIN, MJ .
SCIENCE, 1991, 254 (5031) :579-580
[24]   ON THE EVALUATION OF THE CONSTANT-VM AND CONSTANT-KM IN ENZYME REACTIONS [J].
HOFSTEE, BHJ .
SCIENCE, 1952, 116 (3013) :329-331
[25]   DAILY PATTERNS OF SEROTONIN UPTAKE IN PLATELETS FROM PSYCHIATRIC-PATIENTS AND CONTROL VOLUNTEERS [J].
HUMPHRIES, LL ;
SHIRLEY, P ;
ALLEN, M ;
CODD, EE ;
WALKER, RF .
BIOLOGICAL PSYCHIATRY, 1985, 20 (10) :1073-1081
[26]   THE REGULATION OF GLUCOSE-TRANSPORT IN INSULIN-SENSITIVE CELLS [J].
JOOST, HG ;
WEBER, TM .
DIABETOLOGIA, 1989, 32 (12) :831-838
[27]   NONEQUIVALENT EFFECTS OF PKC ACTIVATION BY PMA ON MURINE CD4 AND CD8 CELL-SURFACE EXPRESSION [J].
KALDJIAN, E ;
MCCARTHY, SA ;
SHARROW, SO ;
LITTMAN, DR ;
KLAUSNER, RD ;
SINGER, A .
FASEB JOURNAL, 1988, 2 (12) :2801-2806
[28]   REDUCED VMAX OF H-3-LABELED SEROTONIN UPTAKE BUT UNCHANGED H-3-IMIPRAMINE BINDING IN THE PLATELETS OF UNTREATED HYPERTENSIVE SUBJECTS [J].
KAMAL, LA ;
RAISMAN, R ;
MEYER, P ;
LANGER, SZ .
LIFE SCIENCES, 1984, 34 (21) :2083-2088
[29]  
KING WG, 1989, J BIOL CHEM, V264, P6070
[30]   RAPID INTERNALIZATION OF THE TRANSFERRIN RECEPTOR IN K562 CELLS IS TRIGGERED BY LIGAND-BINDING OR TREATMENT WITH A PHORBOL ESTER [J].
KLAUSNER, RD ;
HARFORD, J ;
VANRENSWOUDE, J .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES, 1984, 81 (10) :3005-3009