beta-Adrenergic modulation of muscarinic cholinergic receptor expression and function in developing heart.
Imbalances of beta-adrenoceptor (beta-AR) and muscarinic ACh receptor (mAChR) input are thought to underlie perinatal cardiovascular abnormalities in conditions such as sudden infant death syndrome. Administration of isoproterenol, a beta(1)/beta(2)-AR agonist, to neonatal rats on postnatal days (PN) 2-5 caused downregulation of cardiac m(2)AChRs and a corresponding decrement in their control of adenylyl cyclase activity. Terbutaline, a beta(2)-selective agonist that crosses the placenta and the blood-brain barrier, was also effective when given either on PN 2-5 or during gestational days 17-20. Terbutaline failed to downregulate brain m(2)AChRs, even though it downregulated beta-ARs; beta-ARs and m(2)AChRs are located on different cell populations in the brain, but they are on the same cells in the heart. Destruction of catecholaminergic neurons with neonatal 6-hydroxydopamine upregulated cardiac but not brain m(2)AChRs. These results suggest that perinatal beta-AR stimulation shifts cardiac receptor production away from the generation of m(2)AChRs so that the development of sympathetic innervation acts as a negative modulator of cholinergic function. Accordingly, tocolytic therapy with beta-AR agonists may compromise the perinatal balance of adrenergic and cholinergic inputs.
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Related Subject Headings
- Terbutaline
- Receptors, Muscarinic
- Receptors, Adrenergic, beta
- Receptor, Muscarinic M2
- Receptor Cross-Talk
- Rats, Sprague-Dawley
- Rats
- Physiology
- Oxidopamine
- Myocardium
Citation
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Terbutaline
- Receptors, Muscarinic
- Receptors, Adrenergic, beta
- Receptor, Muscarinic M2
- Receptor Cross-Talk
- Rats, Sprague-Dawley
- Rats
- Physiology
- Oxidopamine
- Myocardium