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Muscarinic cholinoceptor activation modulates DNA synthesis and CD40 expression in fibroblast cells
- Source :
- Autonomic and Autacoid Pharmacology. 26:293-301
- Publication Year :
- 2006
- Publisher :
- Wiley, 2006.
-
Abstract
- 1 The aim of the present work was to examine the role of muscarinic acetylcholine receptors (mAChR) on DNA synthesis and CD40 expression in human fibroblast cells. Neonatal human skin fibroblast cultures were stimulated with carbachol in presence or absence of specific antagonists and the following parameters were measured: identification of mAChR subtypes, DNA synthesis, inositol phosphates (InsP) production and CD40 expression. 2 Human fibroblasts express mAChR with Kd 0.47 ± 0.11 nm and Bmax 236 ± 22 fmol mg protein-1. Carbachol stimulates DNA synthesis, InsP and the expression of CD40. All these effects were inhibited by atropine, mustard hydrochloride (4-DAMP) and pirenzepine but not by AF-DX 116 and tropicamide, indicating that M3 and M1 mAChR are implicated in carbachol action. The relative Ki of the antagonists obtained by competition binding assay was in parallel to the relative potency for blocking both carbachol-stimulated InsP accumulation and DNA synthesis. 3 The intracellular pathway leading to carbachol-induced biological effects involved phospholipase C and calcium/calmodulin, as U-73122 and trifluoroperazine blocked carbachol effects, respectively. Calphostin C, a protein kinase C inhibitor, had no effect, indicating that this enzyme does not participate in the system. 4 These results may contribute to a better understanding of the modulatory role of the parasympathetic muscarinic system on normal human fibroblast function. Fil: Casanova, M.. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Furlán, C.. Universidad de Buenos Aires. Facultad de Odontología; Argentina Fil: Sterin, Leonor Josefina. Universidad de Buenos Aires. Facultad de Odontología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina Fil: Borda, Enri Santiago. Universidad de Buenos Aires. Facultad de Odontología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
- Subjects :
- Atropine
Radioligand Assay
chemistry.chemical_compound
Muscarinic acetylcholine receptor
Inositol
Enzyme Inhibitors
Estrenes
INOSITOL PHOSPHATES
CULTURE ASSAY
Cells, Cultured
Flow Cytometry
Receptors, Muscarinic
CHOLINOCEPTORS
Pyrrolidinones
Trifluoperazine
Cell biology
Quinuclidinyl Benzilate
Medicina Básica
medicine.anatomical_structure
CD40 PROTEIN
medicine.drug
CIENCIAS MÉDICAS Y DE LA SALUD
Carbachol
RADIOLIGAND BINDING
Inositol Phosphates
Inmunología
Muscarinic Antagonists
Muscarinic Agonists
Biology
PHOSPHOLIPASE C
Calmodulin
medicine
Humans
Calphostin
CD40 Antigens
Fibroblast
Receptor, Muscarinic M3
Pharmacology
Dose-Response Relationship, Drug
DNA synthesis
Phospholipase C
Receptor, Muscarinic M1
DNA
Pirenzepine
Fibroblasts
Molecular biology
chemistry
Type C Phospholipases
Subjects
Details
- ISSN :
- 14748673 and 14748665
- Volume :
- 26
- Database :
- OpenAIRE
- Journal :
- Autonomic and Autacoid Pharmacology
- Accession number :
- edsair.doi.dedup.....3db245394f71350435c5ce6b9690bb6c