Mechanisms involved in the regulation of mRNA for M2 muscarinic acetylcholine receptors and endothelial and neuronal NO synthases in rat atria
| Autor: | Ganzinelli, S, Joensen, L, Borda, E, Bernabeo, G, Sterin-Borda, L |
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| Jazyk: | angličtina |
| Rok vydání: | 2007 |
| Předmět: |
Male
Nitric Oxide Synthase Type III Nitric Oxide Synthase Type I Cholinergic Agonists In Vitro Techniques Naphthalenes Phosphatidylinositols Mice Animals Heart Atria RNA Messenger Estrenes Rats Wistar Mice Knockout Receptor Muscarinic M2 omega-N-Methylarginine Dose-Response Relationship Drug Reverse Transcriptase Polymerase Chain Reaction Myocardium Heart Research Papers Pyrrolidinones Trifluoperazine Rats Mice Inbred C57BL Gene Expression Regulation Type C Phospholipases Carbachol |
| Popis: | Agonists of the M(2) muscarinic acetylcholine receptor (mAChR) increase mRNA for this receptor and mRNA for endothelial and neuronal isoforms of NO synthase (eNOS or nNOS). Here we examine the different signalling pathways involved in such events in rat cardiac atria.In isolated atria, the effects of carbachol on mRNA for M(2) receptors, eNOS and nNOS were measured along with changes in phosphoinositide (PI) turnover, translocation of protein kinase C (PKC), NOS activity and atrial contractility.Carbachol increased mRNA for M(2) receptors, activation of PI turnover, translocation of PKC and NOS activity and decreased atrial contractility. Inhibitors of phospholipase C (PLC), calcium/calmodulin (CaM), NOS and PKC prevented the carbachol-dependent increase in mRNA for M(2) receptors. These inhibitors also attenuated the carbachol induced increase in nNOS- and eNOS-mRNA levels. Inhibition of nNOS shifted the dose response curve of carbachol on contractility to the right, whereas inhibition of eNOS shifted it to the left.From our results, activation of M(2) receptors induced nNOS and eNOS expression and activation of NOS up-regulated M(2) receptor gene expression. The signalling pathways involved included stimulation of PI turnover via PLC activation, CaM and PKC. nNOS and eNOS mediated opposing effects on the negative inotropic effect in atria, induced by stimulation of M(2) receptors. These results may contribute to a better understanding of the effects and side effects of cholinomimetic treatment in patients with cardiac neuromyopathy. |
| Databáze: | OpenAIRE |
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