       Document 0478
 DOCN  M9460478
 TI    Effects of the HIV-1 envelope glycoprotein gp120 in cerebellar cultures.
       [Ca2+]i increases in a glial cell subpopulation.
 DT    9404
 AU    Ciardo A; Meldolesi J; Department of Pharmacology, Dibit S. Raffaele
       Scientific; Institute, University of Milan, Italy.
 SO    Eur J Neurosci. 1993 Dec 1;5(12):1711-8. Unique Identifier : AIDSLINE
       MED/94170159
 AB    The various types of cells present in cultures prepared from the
       postnatal rat cerebellum, identified by their gross morphology and
       immunocytochemistry, were loaded with the specific dye fura-2 and
       analysed individually for [Ca2+]i changes induced by the HIV-1 envelope
       glycoprotein gp120 and a variety of other treatments. In granule neurons
       [Ca2+]i increases were induced by high KCl and glutamate (mainly through
       the NMDA receptor) while in type-1 astrocytes this effect was observed
       after serotonin, carbachol and also quisqualate. In contrast,
       administration of gp120 was always without effect in these cells. Type-2
       astrocytes (an arborized cell type responsive to agonists targeted to
       the glutamatergic AMPA and cholinergic receptors) were also most often
       unresponsive to the viral glycoprotein. However, among the cells
       exhibiting the arborized phenotype, a subpopulation (approximately 13%)
       responded to gp120 with conspicuous [Ca2+]i increases sustained by both
       release from intracellular stores and influx across the plasma membrane.
       These responses to the viral protein did not involve activation of
       either voltage-gated Ca2+ channels or glutamatergic receptors. Although
       not yet conclusively identified by specific cytochemical markers, the
       gp120-responsive cells resemble type-2 astrocytes and differ from
       neurons and type-1 astrocytes both in gross phenotype and in a number of
       receptor/channel properties: positivity to AMPA and cholinergic
       agonists; negativity to NMDA, serotonin and high KCl. From these results
       it is concluded that a subpopulation of glial cells is affected by
       gp120. The role of these cells in HIV brain infection and damage
       requires further studies to be precisely established.
 DE    Amino Acid Sequence  Animal  Animals, Newborn/PHYSIOLOGY
       Astrocytes/DRUG EFFECTS  Calcium/METABOLISM  Cells, Cultured
       Cerebellum/CYTOLOGY/*DRUG EFFECTS  Cytoplasmic Granules/DRUG EFFECTS
       Fluorescent Antibody Technique  HIV Envelope Protein gp120/*PHARMACOLOGY
       HIV-1/*METABOLISM  Immunohistochemistry  Molecular Sequence Data  Nerve
       Tissue Proteins/IMMUNOLOGY  Neuroglia/*DRUG EFFECTS  Rats  Rats,
       Sprague-Dawley  Support, Non-U.S. Gov't  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

