PMID- 1323259
OWN - NLM
STAT- MEDLINE
DCOM- 19920904
LR  - 20190902
IS  - 0300-8428 (Print)
IS  - 0300-8428 (Linking)
VI  - 87 Suppl 1
DP  - 1992
TI  - Changes in the receptor-G protein-adenylyl cyclase system in heart failure from 
      various types of heart muscle disease.
PG  - 15-35
AB  - The abnormalities of the receptor-G protein-adenylyl cyclase (RCG) system in 
      failing human myocardium as the result of 1) idiopathic dilated cardiomyopathy 
      (IDC), 2) ischemic dilated cardiomyopathy (ISCDC), and 3) primary pulmonary 
      hypertension (PPH) were investigated. Depending on the etiology of heart failure, 
      abnormalities of the RCG system result from a reduced number of beta 1 receptors, 
      uncoupling of beta 1 or beta 2 receptors, alteration of G protein function, or 
      decreased catalytic subunit activity of adenylyl cyclase. Compared to IDC, beta 1 
      receptor down-regulation is less pronounced in ISCDC, and slightly more 
      pronounced in PPH. Preliminary data suggest that beta 1 receptor down-regulation 
      results from alteration in steady-state receptor mRNA levels. Increased 
      functional activity of Gi protein, which seems to result from posttranslational 
      modification, is observed in IDC and ISCDC. Altered Gi protein function may be 
      the basis for beta-receptor uncoupling in IDC and ISCDC, whereas in PPH, this 
      phenomenon may result from altered adenylyl cyclase function. Catalytic subunit 
      activity of adenylyl cyclase is decreased in order of increasing pulmonary 
      hypertension in right-ventricular preparations from PPH greater than IDC greater 
      than ISCDC. However, catalytic subunit activity is similar in LV preparations 
      from all three groups. The decrease in adenylyl cyclase catalytic subunit 
      activity may be the result of the marked cellular injury produced by pressure 
      overload. In summary, numerous desensitization phenomena occur in the failing 
      human heart that are etiology- or model-dependent. To a certain extent, these 
      changes are teleologically beneficial, as they are able to partially protect the 
      failing heart from potentially toxic adrenergic stimuli.
FAU - Bristow, M R
AU  - Bristow MR
AD  - Division of Cardiology, University of Colorado School of Medicine, Denver.
FAU - Feldman, A M
AU  - Feldman AM
LA  - eng
PT  - Journal Article
PT  - Review
PL  - Germany
TA  - Basic Res Cardiol
JT  - Basic research in cardiology
JID - 0360342
RN  - 0 (Receptors, Adrenergic, beta)
RN  - EC 3.6.1.- (GTP-Binding Proteins)
RN  - EC 4.6.1.1 (Adenylyl Cyclases)
SB  - IM
MH  - Adenylyl Cyclases/*metabolism
MH  - Cardiomyopathies/*physiopathology
MH  - Cardiomyopathy, Dilated/physiopathology
MH  - Down-Regulation
MH  - GTP-Binding Proteins/*metabolism
MH  - Heart/*physiopathology
MH  - Humans
MH  - Hypertension, Pulmonary/physiopathology
MH  - Receptors, Adrenergic, beta/*metabolism
RF  - 42
EDAT- 1992/01/01 00:00
MHDA- 1992/01/01 00:01
CRDT- 1992/01/01 00:00
PHST- 1992/01/01 00:00 [pubmed]
PHST- 1992/01/01 00:01 [medline]
PHST- 1992/01/01 00:00 [entrez]
AID - 10.1007/978-3-642-72474-9_2 [doi]
PST - ppublish
SO  - Basic Res Cardiol. 1992;87 Suppl 1:15-35. doi: 10.1007/978-3-642-72474-9_2.