Regionally distinct regulation of astroglial neurotransmitter receptors by fibroblast growth factor-2.
Fibroblast growth factor (FGF)-2 is an abundant astroglial cytokine. We have previously shown that FGF-2 downregulates gap junctions in primary astroglial cultures (B. Reuss et al., 1998, Glia 22, 19-30). We demonstrate now that FGF-2 induces astroglial dopamine (DA) sensitivity and D1 dopamine-receptor (D1DR) antigen and message in cortical and striatal astroglial cultures. On the functional level 10 micromol/L DA triggered transient increases in astroglial [Ca(2+)](i). In gap-junction-coupled cells, no FGF-2-dependent changes in proportions of DA-responsive cells were observable. However, uncoupling with octanol or 18alpha-glycirrhetinic acid isolated the smaller population of astrocytes intrinsically sensitive to DA which was significantly increased by FGF-2 in cortical and striatal cultures. Administration of DR-specific substances revealed that FGF-2 upregulated D1DR. These results indicate that downregulation of astroglial gap junctions by FGF-2 is accompanied by an upregulation of D1DR and DA sensitivity, adding a new aspect to the role of FGF-2 in the regulation of brain functions.
Reuss
B
B
Neuroanatomy, University of Heidelberg, Im Neuenheimer Feld 307, Heidelberg, D-69120, Germany.
Leung
D S
DS
Ohlemeyer
C
C
Kettenmann
H
H
Unsicker
K
K
D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002452:Cell Count / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D003342:Corpus Striatum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism* / Q000494:pharmacology; D017629:Gap Junctions / Q000187:drug effects / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism / Q000494:pharmacology; D006034:Glycyrrhetinic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D007424:Intracellular Fluid / Q000187:drug effects / Q000378:metabolism; D008636:Mesencephalon / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D000442:Octanols / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017447:Receptors, Dopamine D1 / Q000819:agonists / Q000096:biosynthesis / Q000235:genetics; D017981:Receptors, Neurotransmitter / Q000378:metabolism*
D018491:Dopamine Agonists; D000442:Octanols; D012333:RNA, Messenger; D017447:Receptors, Dopamine D1; D017981:Receptors, Neurotransmitter; D016222:Fibroblast Growth Factor 2; C119129:18alpha-glycyrrhetinic acid; D018698:Glutamic Acid; D006034:Glycyrrhetinic Acid; D002118:Calcium; D004298:Dopamine