Endogenous noradrenaline and beta-adrenoceptor regulation in cultured heart cells.
a) Cultured heart muscle cells from chicken embryos and neonatal rats possess about 5000 beta 1-adrenoceptors/cell, heart non muscle cells from these species about 3000 beta 2-adrenoceptors/cell. Agonist binding in heart muscle cells results in cAMP formation and in a positive inotropic effect. b) Beta 1- and beta 2-adrenoceptors of heart cells are downregulated to different degrees in the presence of physiological noradrenaline concentrations in the culture medium. c) Using chicken heart cells in culture, a cellular model of the beta-blocker withdrawal phenomenon in the heart has been established, elucidating the modifying action of endogenous catecholamines and the role of ISA (partial agonist activity) in this phenomenon and classifying the so-called "beta 2-pseudo-selectivity" of the ISA action. d) In the absence of added catecholamines, (-)propranolol exposure of the cells for 3 days increases the number of beta-adrenoceptors of chicken heart muscle cells up to 170% of control, while in rat heart muscle cells the receptor number remains unchanged. The mechanism of this "basal" receptor downregulation in chicken heart muscle cells is unclear. The data presented demonstrate the usefulness of heart cell cultures in the study of beta-adrenoceptor regulation of the heart.
Reithmann
C
C
Medizinische Klinik I, Universität München, Klinikum Grosshadern, F.R.G.
Thomschke
A
A
Werdan
K
K
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D002642:Chick Embryo; D000242:Cyclic AMP / Q000096:biosynthesis; D007545:Isoproterenol / Q000494:pharmacology; D009206:Myocardium / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism*
D011943:Receptors, Adrenergic, beta; D011433:Propranolol; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D007545:Isoproterenol; D009638:Norepinephrine