Adrenergic and muscarinic receptor regulation and therapeutic implications in heart failure.
In end-stage heart failure the expression of different myocardial regulatory proteins involved in the beta-adrenergic cAMP signalling pathway is altered. The downregulation of beta 1-adrenoceptors and their uncoupling from the effector as well as an increased expression of the inhibitory GTP-binding protein seem to be the most important alterations. Since catecholamine levels are elevated in these patients and since some alterations can be 'restored' after treatment with beta-adrenoceptor antagonists it was hypothesized that excessive beta-adrenergic stimulation could be involved in these alterations. In this article the changes of beta-adrenergic receptors, GTP-binding proteins, sarcoplasmic reticulum Ca(2+)-ATPase and of phospholamban found in heart failure are addressed with its possible therapeutic implications.
Schmitz
W
W
Institut für Pharmakologie und Toxikologie, Westfälische Wilhelms-Universität, Münster, Germany.
Boknik
P
P
Linck
B
B
Müller
F U
FU
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology* / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D002135:Calcium-Binding Proteins / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D015536:Down-Regulation; D019204:GTP-Binding Proteins / Q000378:metabolism; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D009206:Myocardium / Q000378:metabolism; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use*; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D018342:Receptors, Adrenergic, beta-1 / Q000096:biosynthesis / Q000502:physiology; D011976:Receptors, Muscarinic / Q000502:physiology*; D012519:Sarcoplasmic Reticulum / Q000201:enzymology; D015398:Signal Transduction; D000099211:Phospholamban
D000319:Adrenergic beta-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D002135:Calcium-Binding Proteins; D000252:Calcium-Transporting ATPases; D019204:GTP-Binding Proteins; D010726:Phosphodiesterase Inhibitors; D011943:Receptors, Adrenergic, beta; D018342:Receptors, Adrenergic, beta-1; D011976:Receptors, Muscarinic; D000099211:Phospholamban