title: Acetylcholine as a mitogen: muscarinic receptor-mediated proliferation of rat astrocytes and human astrocytoma cells.
abstract: The mitogenic effect of muscarinic receptor agonists in glial cells has been characterized in rat cortical astrocytes and human 132 1N1 astrocytoma cells. The muscarinic receptor agonist carbachol caused a dose- and time-dependent increase in proliferation, as measured by [3H]thymidine incorporation. The mitogenic effect was mimicked by several muscarinic, but not nicotinic receptor agonists, and was blocked by muscarinic receptor antagonists. Reverse transcription-polymerase chain reaction (RT-PCR) experiments indicated the presence of m2, m3 and to a lesser degree, m5 muscarinic receptor mRNA in both astrocytes and astrocytoma cells. Proliferation experiments with subtype-specific muscarinic receptor antagonists suggest that carbachol-induced proliferation is due to activation of muscarinic M3 receptors. The phorbol ester 12-O-tetradecanoyl-phorbol 13-acetate (TPA) also stimulated glial cell proliferation. Down-regulation of protein kinase C, or the protein kinase C antagonist 1,5-(isoquinolynsulfanyl)-2-methylpiperazine dihydrochloride (H7) blocked proliferation induced by either TPA or carbachol. Of other neurotransmitters tested, histamine caused glial cell proliferation, norepinephrine and gamma-aminobutyric acid were ineffective, while serotonin and glutamate inhibited basal or serum-stimulated proliferation.
authors.affiliation: Department of Environmental Health, University of Washington, Seattle, 98105, USA.
authors.forename: M
authors.initials: M
authors.lastname: Guizzetti
authors.forename: P
authors.initials: P
authors.lastname: Costa
authors.forename: J
authors.initials: J
authors.lastname: Peters
authors.forename: L G
authors.initials: LG
authors.lastname: Costa
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D001253:Astrocytes / Q000166:cytology*; D001254:Astrocytoma / Q000473:pathology*; D001483:Base Sequence; D002455:Cell Division / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D017931:DNA Primers; D005260:Female; D006801:Humans; D008934:Mitogens / Q000494:pharmacology*; D008969:Molecular Sequence Data; D018721:Muscarinic Agonists / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D014407:Tumor Cells, Cultured
chemical_list: D017931:DNA Primers; D008934:Mitogens; D018721:Muscarinic Agonists; D018722:Nicotinic Agonists; D012333:RNA, Messenger; D011976:Receptors, Muscarinic; D000109:Acetylcholine