Decrease in the Sensitivity of Myocardium to M3 Muscarinic Receptor Stimulation during Postnatal Ontogenisis
| Autor: | S. V. Tapilina, Denis V. Abramochkin |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Muscarinic acetylcholine receptor M3 Muscarinic acetylcholine receptor M2 Stimulation Muscarinic acetylcholine receptor M1 Biochemistry Muscarinic agonist 03 medical and health sciences chemistry.chemical_compound 030104 developmental biology 0302 clinical medicine Endocrinology chemistry Internal medicine Muscarinic acetylcholine receptor cardiovascular system medicine Methoctramine Muscarinic acetylcholine receptor M4 Molecular Medicine Molecular Biology 030217 neurology & neurosurgery Biotechnology |
| Zdroj: | Acta Naturae. 8:127-131 |
| ISSN: | 2075-8251 |
| Popis: | Type 3 muscarinic receptors (M3 receptors) participate in the mediation of cholinergic effects in mammalian myocardium, along with M2 receptors. However, myocardium of adult mammals demonstrates only modest electrophysiological effects in response to selective stimulation of M3 receptors which are hardly comparable to the effects produced by M2 stimulation. In the present study, the effects of selective M3 stimulation induced by application of the muscarinic agonist pilocarpine (10 M) in the presence of the selective M2 blocker methoctramine (100 nM) on the action potential (AP) waveform were investigated in isolated atrial and ventricular preparations from newborn and 3-week-old rats and compared to those in preparations from adult rats. In the atrial myocardium, stimulation of M3 receptors produced a comparable reduction of AP duration in newborn and adult rats, while in 3-week-old rats the effect was negligible. In ventricular myocardial preparations from newborn rats, the effect of M3 stimulation was more than 3 times stronger compared to that from adult rats, while preparations from 3-week old rats demonstrated no definite effect, similarly to atrial preparations. In all studied types of cardiac preparations, the effects of M3 stimulation were eliminated by the selective M3 antagonist 4-DAMP (10 nM). The results of RT-PCR show that the amount of product of the M3 receptor gene decreases with the maturation of animals both in atrial and ventricular myocardium. We concluded that the contribution of M3 receptors to the mediation of cardiac cholinergic responses decreases during postnatal ontogenesis. These age-related changes may be associated with downregulation of M3 receptor gene expression. |
| Databáze: | OpenAIRE |
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