Comparative properties of the in ovo and in vitro differentiation of the muscarinic cholinergic receptor in embryonic heart cells
| Autor: | Michel Lazdunski, J.F. Renaud, Jacques Barhanin, D. Cavey, Michel Fosset |
|---|---|
| Rok vydání: | 1980 |
| Předmět: |
medicine.medical_specialty
Chick Embryo Biology Heart Rate Internal medicine Muscarinic acetylcholine receptor M5 Muscarinic acetylcholine receptor Muscarinic acetylcholine receptor M4 medicine Animals Receptors Cholinergic Cyclic GMP Molecular Biology Cells Cultured Myocardium Oxotremorine Muscarinic acetylcholine receptor M3 Heart Muscarinic acetylcholine receptor M2 Cell Biology Muscarinic acetylcholine receptor M1 Myocardial Contraction Receptors Muscarinic Acetylcholine Quinuclidinyl Benzilate Endocrinology Cholinergic Carbachol Developmental Biology medicine.drug |
| Zdroj: | Developmental Biology. 78:184-200 |
| ISSN: | 0012-1606 |
| DOI: | 10.1016/0012-1606(80)90328-0 |
| Popis: | The negative chronotropic response of embryonic hearts to acetylcholine and muscarinic agents increases with age. Differences in cholinergic sensitivity between embryonic hearts at an early or a late stage of development include: (i) a difference in the maximal decrease of the frequency of beating produced by saturating concentrations of the cholinergic agent; (ii) a difference in ID 50 values for muscarinic agonists; (iii) differences in the rates of activation and desensitization of the muscarinic receptor. Different types of physiological responses to cholinergic agents are observed in cultures of embryonic cardiac cells: (i) monolayers of cardiac cells are unresponsive to cholinergic agents; (ii) reaggregates of cardiac cells maintained 3 days in culture display a physiological response to muscarinic agonists; (iii) an in vitro differentiation of the cholinergic response resembling that observed in vivo can be obtained with reaggregates prepared from 11-day-old embryonic hearts and maintained between 2 and 10 days in culture. The in vivo or in vitro development of the negative chronotropic response of cardiac cells to cholinergic agents is not linked to changes in the number of cholinergic receptors. An invariant affinity of the muscarinic receptor for muscarinic antagonists has been found at all stages of development. The number of muscarinic receptors in monolayers of cardiac cells which are physiologically unresponsive to cholinergic agents is higher than that found for cardiac cell reaggregates. Affinities for muscarinic antagonists are the same in the case of monolayers and reaggregates. The rate of degradation of the physiologically unresponsive muscarinic receptor in monolayers follows first-order kinetics with a half-time of 14 hr; the physiologically responsive muscarinic receptor in reaggregates remains perfectly stable 20 hr after blocking protein synthesis. Differentiation of a physiological response to muscarinic agents seems to be clearly linked to molecular events which occur after ligand binding to the muscarinic receptor. It does not seem that a coupling between agonist binding and guanylate cyclase stimulation is necessarily involved. |
| Databáze: | OpenAIRE |
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