Muscarinic cholinergic inhibition of beta-adrenergic stimulation of phospholamban phosphorylation and CaS transport in guinea pig ventricles
The effects of muscarinic cholinergic stimulation on beta-adrenergic induced increases in phospholamban phosphorylation and CaS transport were studied in intact myocardium. Isolated guinea pig ventricles were perfused via the coronary arteries with TSPi, after which membrane vesicles were isolated from individual hearts. Isoproterenol produced reversible increases in TSP incorporation into phospholamban. Associated with the increases in TSP incorporation were increases in the initial rate of phosphate-facilitated CaS uptake measured in aliquots of the same membrane vesicles isolated from the perfused hearts. The increases in TSP incorporation and calcium transport were significantly attenuated by the simultaneous administration of acetylcholine. Acetylcholine also attenuated increases in phospholamban phosphorylation and CaS uptake produced by the phosphodiesterase inhibitor isobutylmethylxanthine and forskolin. The contractile effects of all agents which increased cAMP levels (increased contractility and a reduction in the t1/2 of relaxation) were also attenuated by acetylcholine. The inhibitory effects of acetylcholine were associated with attenuation of the increases in cAMP levels produced by isoproterenol and isobutylmethylxanthine but not by forskolin. Acetylcholine also increased the rate of reversal of the functional and biochemical effects of isoproterenol by propranolol without affecting cAMP levels. These results suggest that cholinergic agonists inhibit the functional effects of beta-adrenergic stimulation in part by inhibition of phospholamban phosphorylation. This inhibition may be mediated by two potential mechanisms: inhibition of beta-adrenergic activation of adenylate cyclase and stimulation of dephosphorylation.
- Research Organization:
- Indiana Univ. School of Medicine, Indianapolis
- OSTI ID:
- 6182026
- Journal Information:
- J. Biol. Chem.; (United States), Journal Name: J. Biol. Chem.; (United States) Vol. 24; ISSN JBCHA
- Country of Publication:
- United States
- Language:
- English
Similar Records
Role of cyclic GMP in cells with the properties of smooth muscle cultured from the rat myometrium
Regulation of phosphorylation of nicotinic acetylcholine receptors in mouse BC3H1 myocytes
Related Subjects
59 BASIC BIOLOGICAL SCIENCES
ACETYLCHOLINE
ALKALINE EARTH METALS
AMINES
AMMONIUM COMPOUNDS
AMP
ANIMALS
ARTERIES
AUTONOMIC NERVOUS SYSTEM AGENTS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL EFFECTS
BLOOD VESSELS
BODY
CALCIUM
CARDIOVASCULAR SYSTEM
CHEMICAL REACTIONS
CORONARIES
DAYS LIVING RADIOISOTOPES
DRUGS
ELEMENTS
ENZYME INHIBITORS
ESTERS
GUINEA PIGS
HEART
ISOTOPES
KINETICS
LIGHT NUCLEI
MAMMALS
MEMBRANE TRANSPORT
METALS
MUSCLES
MYOCARDIUM
NEUROREGULATORS
NUCLEI
NUCLEOTIDES
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
ORGANS
PARASYMPATHOMIMETICS
PERFUSED ORGANS
PHOSPHORUS 32
PHOSPHORUS ISOTOPES
PHOSPHORYLATION
QUATERNARY COMPOUNDS
RADIOISOTOPES
REACTION KINETICS
RODENTS
VERTEBRATES