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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

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

Published Date

  • May 2002

Published In

Volume / Issue

  • 282 / 5

Start / End Page

  • R1356 - R1363

PubMed ID

  • 11959676

International Standard Serial Number (ISSN)

  • 0363-6119

Digital Object Identifier (DOI)

  • 10.1152/ajpregu.00598.2001


  • eng

Conference Location

  • United States