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Published on: February 10, 2013
[Pharmacological characterization of chicken cardiac beta-adrenoceptors]
1Department of Pharmacology, Hokkaido University School of Medicine, Sapporo, Japan.
Abstract:
Pharmacological properties of cardiac beta-adrenoceptors of embryonic chick (16-18 day in ovo), hatched chick (3-5 days after hatching) and adult chicken (20 weeks after hatching) were investigated. Pharmacological analysis using subtype specific agonists and antagonists showed that cardiac beta-adrenoceptors of embryonic chick and hatched chick could not be classified as beta 1- or beta 2-adrenoceptors. Scatchard analysis of specific [125I]-iodocyanopindolol (ICYP) binding revealed ICYP bound to two different population of binding sites (high and low affinity) in all stages; Kd and Bmax of these sites remained unchanged before and after hatching, although Bmax but not Kd was found to increase in adult chicken. Displacement of ICYP with propranolol (a nonspecific beta-antagonist), ICI 118,551 (a specific beta 2-antagonist) and atenolol (a specific beta 1-antagonist) indicated the presence of two affinity binding sites for all of the antagonists. Ki values for these antagonists at the high affinity binding sites were almost identical to pA2 values obtained from their antagonistic effects on isoproterenol inotropic response, suggesting that the high affinity binding sites for ICYP bear the pharmacological significance. Significant increase in sensitivity to the inotropic effects of beta-adrenoceptor agonists was observed in the hatched chick heart, whereas Ki values calculated from displacement of ICYP with these agonists in the presence of GppNHp were not changed. Dobutamine which was a Partial agonist in the embryonic chick heart, was found to behave as a full agonist in the hatched chick heart. These result suggested that chicken cardiac beta-adrenoceptors show different properties from either beta 1- or beta 2-adrenoceptors reported in mammalian hearts, and coupling between binding and adenylate cyclase might be more efficient after hatching.
Insights
Chicken cardiac beta-adrenoceptors differ from mammalian types, showing distinct pharmacological properties before and after hatching. Post-hatching, increased sensitivity and altered agonist efficacy suggest enhanced receptor-effector coupling.
Area of Science:
- Cardiovascular Pharmacology
- Adrenoceptor Research
- Developmental Biology
Context:
- Cardiac beta-adrenoceptors regulate heart function.
- Understanding avian cardiac beta-adrenoceptor subtypes is crucial for comparative pharmacology.
- Developmental changes in receptor properties are not well-characterized in avian species.
Purpose:
- To investigate the pharmacological characteristics of cardiac beta-adrenoceptors in embryonic, hatched, and adult chickens.
- To determine if these receptors can be classified as beta 1- or beta 2-adrenoceptors.
- To analyze developmental changes in receptor binding affinity and agonist/antagonist sensitivity.
Summary:
- Cardiac beta-adrenoceptors in embryonic and hatched chicks could not be classified as beta 1 or beta 2 subtypes.
- Scatchard analysis revealed consistent high and low affinity binding sites, with increased Bmax in adults.
- Sensitivity to beta-adrenoceptor agonists increased post-hatching, with dobutamine shifting from partial to full agonist activity, indicating altered receptor-effector coupling.
Impact:
- Chicken cardiac beta-adrenoceptors exhibit unique properties distinct from mammalian beta 1/beta 2 subtypes.
- Post-hatching development enhances the efficiency of beta-adrenoceptor signaling pathways in the chicken heart.
- Findings provide insights into avian cardiovascular physiology and adrenoceptor evolution.
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