GABAB receptors in Schwann cells influence proliferation and myelin protein expression.
The location and the role of gamma-aminobutyric acid type B (GABA(B)) receptors in the central nervous system have recently received considerable attention, whilst relatively little is known regarding the peripheral nervous system. In this regard, here we demonstrate for the first time that GABA(B) receptor isoforms [i.e. GABA(B(1)) and GABA(B(2))] are specifically localized in the rat Schwann cell population of the sciatic nerve. Using the selective GABA(B) agonist [i.e. (-)-baclofen] and the antagonists (i.e. CGP 62349, CGP 56999 A, CGP 55845 A), such receptors are shown to be functionally active and negatively coupled to the adenylate cyclase system. Furthermore, exposure of cultured Schwann cells to (-)-baclofen inhibits their proliferation and reduces the synthesis of specific myelin proteins (i.e. glycoprotein Po, peripheral myelin protein 22, myelin-associated glycoprotein, connexin 32), providing evidence for a physiological role of GABA(B) receptors in the glial cells of the peripheral nervous system.
Magnaghi
Valerio
V
Department of Endocrinology and Center of Excellence on Neurodegenerative Diseases, University of Milan, Via Balzaretti 9, 20133 Milan, Italy. valerio.magnaghi@unimi.it
Ballabio
Marinella
M
Cavarretta
Ilaria T R
IT
Froestl
Wolfgang
W
Lambert
Jeremy J
JJ
Zucchi
Ileana
I
Melcangi
Roberto C
RC
D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D015152:Blotting, Northern / Q000379:methods; D015153:Blotting, Western / Q000379:methods; D001973:Bromodeoxyuridine / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D007041:Hypoxanthine Phosphoribosyltransferase / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D007211:Indoles / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D009185:Myelin Proteins / Q000235:genetics / Q000378:metabolism*; D020033:Protein Isoforms / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D018080:Receptors, GABA-B / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012583:Schwann Cells / Q000187:drug effects / Q000378:metabolism*; D012584:Sciatic Nerve / Q000166:cytology / Q000378:metabolism; D013778:Tetrazolium Salts / Q000378:metabolism; D013997:Time Factors
D018755:GABA Agonists; D018756:GABA Antagonists; D007211:Indoles; D008565:Membrane Proteins; D009185:Myelin Proteins; C406964:Perp protein, mouse; D020033:Protein Isoforms; D012333:RNA, Messenger; D018080:Receptors, GABA-B; D013778:Tetrazolium Salts; C042207:4-anisyltetrazolium blue; D005576:Colforsin; C007293:DAPI; D000242:Cyclic AMP; D007041:Hypoxanthine Phosphoribosyltransferase; D001973:Bromodeoxyuridine; D001418:Baclofen