Mechanisms of thyroid hormone control over sensitivity and maximal contractile responsiveness to beta-adrenergic agonists in atria.
This paper discusses the mechanisms of two basic effects of thyroid hormones on atrial responses to beta-adrenergic agonists, i.e. increased inotropic sensitivity and decreased maximal contractile responsiveness. The increased sensitivity of atria to beta-adrenergic agonists under thyroid hormones appears to be related to increases in beta-adrenoceptor density and Gs/Gi protein ratio, leading to activation of Gs-mediated pathway, but suppression of Gi-mediated pathway of adenylate cyclase regulation. Therefore, the i/c concentrations of cAMP and corresponding inotropic responses achieve their maximums at lower doses of beta-adrenergic agonist. Thyroid hormones also decrease the expression of phospholamban, but increase the expression of sarcoplasmic reticulum Ca2+-pump. As a result, the basal activity of sarcoplasmic reticulum Ca2+-pump increases, but its beta-adrenergic activation through phosphorylation of phospholamban decreases. It is suggested that these changes are causal for decreased maximal inotropic and lusitropic responses of atria to beta-adrenergic agonists.
Seppet
E K
EK
Department of Pathophysiology, University of Tartu, Estonia.
Kaasik
A
A
Minajeva
A
A
Paju
K
K
Ohisalo
J J
JJ
Vetter
R
R
Braun
U
U
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D016275:Atrial Function; D002135:Calcium-Binding Proteins / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism; D006146:Guanidines / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects*; D010660:Phenylisopropyladenosine / Q000494:pharmacology; D010766:Phosphorylation; D011724:Pyridazines / Q000494:pharmacology; D011760:Pyrrolidinones / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D020889:Rolipram; D013963:Thyroid Hormones / Q000502:physiology*; D000099211:Phospholamban
D000318:Adrenergic beta-Agonists; D002135:Calcium-Binding Proteins; D000252:Calcium-Transporting ATPases; D000242:Cyclic AMP; D019204:GTP-Binding Proteins; D006146:Guanidines; D007545:Isoproterenol; D010660:Phenylisopropyladenosine; D011724:Pyridazines; D011760:Pyrrolidinones; D011943:Receptors, Adrenergic, beta; D020889:Rolipram; D013963:Thyroid Hormones; D000099211:Phospholamban; C056215:siguazodan