A NICOTINIC ACETYLCHOLINE-RECEPTOR REGULATING CELL-ADHESION AND MOTILITY IS EXPRESSED IN HUMAN KERATINOCYTES

被引:177
作者
GRANDO, SA
HORTON, RM
PEREIRA, EFR
DIETHELMOKITA, BM
GEORGE, PM
ALBUQUERQUE, EX
CONTIFINE, BM
机构
[1] UNIV MINNESOTA,SCH MED,DEPT PHARMACOL,MINNEAPOLIS,MN 55455
[2] UNIV MINNESOTA,COLL BIOL SCI,DEPT BIOCHEM,ST PAUL,MN 55108
[3] UNIV MARYLAND,SCH MED,DEPT PHARMACOL & EXPTL THERAPEUT,BALTIMORE,MD 21201
[4] FED UNIV RIO DE JANEIRO,INST BIOFIS CARLOS CHAGAS FILHO,MOLEC PHARMACOL LAB,BR-21945 RIO JANEIRO,BRAZIL
关键词
PATCH CLAMP; RADIOLIGAND BINDING; IMMUNOFLUORESCENCE; POLYMERASE CHAIN REACTION;
D O I
10.1111/1523-1747.ep12325606
中图分类号
R75 [皮肤病学与性病学];
学科分类号
100206 ;
摘要
Acetylcholine is synthesized and released by human epidermal keratinocytes and modulates the adhesion and motility of these cells. To understand the molecular basis of the effects of acetylcholine on keratinocytes, we investigated the presence, pharmacology, structure, and function of nicotinic acetylcholine receptors in human epidermal keratinocytes. Patch-clamp studies indicated that keratinocytes express acetylcholine receptors with ion gating and pharmacologic properties similar to those observed so far only in neurons, and containing the alpha(3) subunit. Specific binding of the receptor-specific ligand I-125-kappa-bungarotoxin revealed approximately 5500 binding sites per cell on undifferentiated keratinocytes in cell cultures and approximately 35,400 binding sites per cell on mature keratinocytes freshly isolated from human neonatal foreskins. Antibody binding and polymerase chain reaction experiments demonstrated the presence of alpha(3), beta(2), and beta(4) nicotinic receptor subunits. Binding of subunit-specific antibodies indicated that nicotinic receptors were associated with the suprabasal keratinocytes in epidermis and localized to the cell membranes of differentiated keratinocytes in cell cultures. Acetylcholine and the nicotinic agonist nicotine increased cell-substrate and cell-cell adherence of cultured keratinocytes and stimulated their lateral migration. The specific antagonists K-bungarotoxin and mecamylamine caused cell detachment and abolished migration. Thus, a nicotinic receptor expressed in keratinocytes may mediate acetylcholine control of keratinocyte adhesion and motility.
引用
收藏
页码:774 / 781
页数:8
相关论文
共 39 条
  • [1] CALCIUM PERMEABILITY AND MODULATION OF NICOTINIC ACETYLCHOLINE RECEPTOR-CHANNELS IN RAT PARASYMPATHETIC NEURONS
    ADAMS, DJ
    NUTTER, TJ
    [J]. JOURNAL OF PHYSIOLOGY-PARIS, 1992, 86 (1-3) : 67 - 76
  • [2] BELLONE M, 1993, J IMMUNOL, V151, P1025
  • [3] FUNCTIONAL EXPRESSION OF 2 NEURONAL NICOTINIC ACETYLCHOLINE-RECEPTORS FROM CDNA CLONES IDENTIFIES A GENE FAMILY
    BOULTER, J
    CONNOLLY, J
    DENERIS, E
    GOLDMAN, D
    HEINEMANN, S
    PATRICK, J
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1987, 84 (21) : 7763 - 7767
  • [4] CAI Z, 1992, METHOD ENZYMOL, V216, P100
  • [5] CHIAPPINELLI VA, 1993, NATURAL SYNTHETIC NE, P65
  • [6] THE NICOTINIC ACETYLCHOLINE-RECEPTOR - STRUCTURE AND AUTOIMMUNE PATHOLOGY
    CONTITRONCONI, BM
    MCLANE, KE
    RAFTERY, MA
    GRANDO, SA
    PROTTI, MP
    [J]. CRITICAL REVIEWS IN BIOCHEMISTRY AND MOLECULAR BIOLOGY, 1994, 29 (02) : 69 - 123
  • [7] FUNCTIONAL STABILITY OF TORPEDO ACETYLCHOLINE-RECEPTOR - EFFECTS OF PROTEASE TREATMENT
    CONTITRONCONI, BM
    DUNN, SMJ
    RAFTERY, MA
    [J]. BIOCHEMISTRY, 1982, 21 (05) : 893 - 899
  • [8] LOW-AFFINITY MIXED ACETYLCHOLINE-RESPONSIVE RECEPTORS AT THE APICAL MEMBRANE OF FROG TADPOLE SKIN
    COX, TC
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY, 1993, 264 (03): : C552 - C558
  • [9] DECKER ER, 1990, J NEUROSCI, V10, P3413
  • [10] THE FUNCTIONAL DIVERSITY OF THE NEURONAL NICOTINIC ACETYLCHOLINE-RECEPTORS IS INCREASED BY A NOVEL SUBUNIT - BETA-4
    DUVOISIN, RM
    DENERIS, ES
    PATRICK, J
    HEINEMANN, S
    [J]. NEURON, 1989, 3 (04) : 487 - 496