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Non-co-ordinate development of beta-adrenergic receptors and adenylate cyclase in chick heart
Abstract:
We have studied the properties of beta-adrenergic receptors and of their interaction with adenylate cyclase in the chick myocardium during embryogenesis. Between 4.5 and 7.5 days in ovo the number of receptors determined by (-)-[3H]dihydroalprenolol ([3H]DHA) binding is constant at approx. 0.36 pmol of receptor/mg of protein. By day 9 the density decreases significantly to 0.22 pmol of receptor/mg of protein. At day 12.5--13.5 the number was 0.14--0.18 pmol of receptor/mg of protein. This number did not change further up to day 16. The same results were obtained with guanosine 5'-[beta, gamma-imido]triphosphate (p[NH]ppG) added to the assay mixtures. There was no significant change in receptor affinity for the antagonist [3H]DHA between days 5.5 and 13. Despite the decrease in numbers of beta-adrenergic receptors, there was no change in basal, p[NH]ppG-, isoprenaline- or isoprenaline-plus-p[NH]ppG-stimulated adenylate cyclase activity between days 3 and 12 of development. We conclude that beta-adrenergic receptors and adenylate cyclase are not co-ordinately regulated during early embryonic development of the chick heart. Some of the beta-adrenergic receptors present very early in the ontogeny of cardiac tissue appear not to be coupled to adenylate cyclase since their loss is not reflected in decreased activation of the enzyme.
Insights
During chick heart development, beta-adrenergic receptors decrease significantly after 7.5 days. However, adenylate cyclase activity remains unchanged, indicating uncoupled receptor regulation.
Area of Science:
- Developmental Biology
- Cardiovascular Physiology
- Molecular Pharmacology
Background:
- Beta-adrenergic receptors (β-ARs) are crucial for cardiac function.
- Their interaction with adenylate cyclase (AC) regulates cellular responses.
- Understanding their developmental regulation is key to cardiac ontogeny.
Purpose of the Study:
- To investigate the developmental changes in β-ARs and their functional coupling to AC in the embryonic chick myocardium.
- To determine if β-ARs and AC are co-regulated during cardiac embryogenesis.
Main Methods:
- Quantification of β-ARs using (-)-[3H]dihydroalprenolol ([3H]DHA) binding assays.
- Measurement of adenylate cyclase activity under basal and stimulated conditions (p[NH]ppG, isoprenaline).
- Analysis of receptor-ligand affinity and receptor density across different embryonic days.
Main Results:
- β-AR density significantly decreased from 7.5 days of incubation onwards, while receptor affinity remained constant.
- Despite the decline in β-AR numbers, basal and stimulated adenylate cyclase activity showed no significant changes throughout development.
- Guanylylimidodiphosphate (p[NH]ppG) did not alter receptor affinity or density.
Conclusions:
- Beta-adrenergic receptors and adenylate cyclase are not co-ordinately regulated in the developing chick heart.
- A portion of early embryonic cardiac β-ARs may not be functionally coupled to adenylate cyclase.