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.
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Authors | M Guizzetti, P Costa, J Peters, L G Costa |
Journal | European journal of pharmacology
(Eur J Pharmacol)
Vol. 297
Issue 3
Pg. 265-73
(Feb 22 1996)
ISSN: 0014-2999 [Print] Netherlands |
PMID | 8666059
(Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- DNA Primers
- Mitogens
- Muscarinic Agonists
- Nicotinic Agonists
- RNA, Messenger
- Receptors, Muscarinic
- Acetylcholine
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Topics |
- Acetylcholine
(pharmacology)
- Animals
- Astrocytes
(cytology)
- Astrocytoma
(pathology)
- Base Sequence
- Cell Division
(drug effects, physiology)
- Cells, Cultured
- DNA Primers
- Female
- Humans
- Mitogens
(pharmacology)
- Molecular Sequence Data
- Muscarinic Agonists
(pharmacology)
- Nicotinic Agonists
(pharmacology)
- Pregnancy
- RNA, Messenger
(genetics)
- Rats
- Rats, Sprague-Dawley
- Receptors, Muscarinic
(drug effects, genetics, physiology)
- Tumor Cells, Cultured
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