TY - JOUR
T1 - Acetylcholine as a mitogen
T2 - Muscarinic receptor-mediated proliferation of rat astrocytes and human astrocytoma cells
AU - Guizzetti, Marina
AU - Costa, Paola
AU - Peters, Janet
AU - Costa, Lucio G.
N1 - Funding Information:
This study was supported by a grant from NIAAA (AA-08154) and from the Alcohol and Drug Abuse Institute, University of Washington. We thank Drs J.H. Brown and D. Goldstein (University of California, San Diego) for donating the 132 1N1 astrocytoma cells and Ms. Chris Sievanen for secretarial assistance.
PY - 1996/2/22
Y1 - 1996/2/22
N2 - 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 γ-aminobutyric acid were ineffective, while serotonin and glutamate inhibited basal or serum-stimulated proliferation.
AB - 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 γ-aminobutyric acid were ineffective, while serotonin and glutamate inhibited basal or serum-stimulated proliferation.
KW - Astrocyte
KW - Astrocytoma
KW - Cell proliferation
KW - Muscarinic receptor
UR - http://www.scopus.com/inward/record.url?scp=0030064643&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0030064643&partnerID=8YFLogxK
U2 - 10.1016/0014-2999(95)00746-6
DO - 10.1016/0014-2999(95)00746-6
M3 - Article
C2 - 8666059
AN - SCOPUS:0030064643
SN - 0014-2999
VL - 297
SP - 265
EP - 273
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
IS - 3
ER -