Increase in functional activity rather than in amount of Gi-alpha in failing human heart with dilated cardiomyopathy.
OBJECTIVE
The aim was to investigate whether or not increased pertussis toxin catalysed ADP ribosylation correlates with increased amount of Gi-alpha in failing human heart.


METHODS
Antisera raised against unique synthetic peptides corresponding to alpha subunits of Gs and Gi 1-3 were used in immunoblotting and ELISA to determine amounts of various G proteins. Adenylyl cyclase activity, beta adrenoceptors, and muscarinic receptors were then measured in cardiomyopathic hearts (n = 6) obtained at transplant in order to study whether or not an altered expression of G proteins has relevance to the integrity and function of the receptor--adenylyl cyclase system. Six non-failing control hearts were also studied.


RESULTS
No significant differences in the peptide equivalent amounts of either Gs or Gi were found in the failing human heart as compared to the non-failing heart. However, functional activity of Gi was shown to increase significantly since there was a decrease in basal (57%), isoprenaline stimulated (60%), and guanyliminodiphosphate stimulated (52%) adenylyl cyclase activity. In contrast the density of beta adrenoceptors was markedly decreased (51%) in failing human heart in comparison to non-failing hearts. Neither the density nor the affinity of muscarinic receptors changed in the failing human heart.


CONCLUSIONS
These results suggest that in the failing human heart, there is an increase in functional activity rather than in amount of Gi, and an important part of functional expression of Gi-alpha may be regulated at the post-translational level.
Fu
L X
LX
Wallenberg Laboratory, Sahlgren's Hospital, University of Göteborg, Sweden.
Liang
Q M
QM
Waagstein
F
F
Hoebeke
J
J
Sylvén
C
C
Jansson
E
E
Sotonyi
P
P
Hjalmarson
A
A
D000262:Adenylyl Cyclases / Q000378:metabolism; D002311:Cardiomyopathy, Dilated / Q000378:metabolism / Q000503:physiopathology*; D004797:Enzyme-Linked Immunosorbent Assay; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006321:Heart / Q000503:physiopathology*; D006801:Humans; D015151:Immunoblotting; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000378:metabolism
D011943:Receptors, Adrenergic, beta; D011976:Receptors, Muscarinic; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases