β-Adrenergic modulation of muscarinic cholinergic receptor expression and function in developing heart

Published

Journal Article

Imbalances of β-adrenoceptor (β-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 β1/β2-AR agonist, to neonatal rats on postnatal days (PN) 2-5 caused downregulation of cardiac m2AChRs and a corresponding decrement in their control of adenylyl cyclase activity. Terbutaline, a β2-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 down-regulate brain m2AChRs, even though it downregulated β-ARs; β-ARs and m2AChRs 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 m2AChRs. These results suggest that perinatal β-AR stimulation shifts cardiac receptor production away from the generation of m2AChRs so that the development of sympathetic innervation acts as a negative modulator of cholinergic function. Accordingly, tocolytic therapy with β-AR agonists may compromise the perinatal balance of adrenergic and cholinergic inputs.

Duke Authors

Cited Authors

  • Garofolo, MC; Seidler, FJ; Auman, JT; Slotkin, TA

Published Date

  • July 2, 2002

Published In

Volume / Issue

  • 282 / 5 51-5

International Standard Serial Number (ISSN)

  • 0363-6119

Citation Source

  • Scopus