Characteristics of the beta-adrenergic receptor complex in the epicardial border zone of the 5-day infarcted canine heart.
BACKGROUND
The effect of isoproterenol on increasing the peak amplitude of the L-type calcium current is reduced in myocytes dispersed from the epicardial border zone (EBZ) of the 5-day infarcted canine heart when compared with control cells from noninfarcted hearts. This suggests that specific alterations in the beta-adrenergic receptor complex develop in this setting. The present study is an examination of individual components of the beta-adrenergic receptor complex with the aim of elucidating the biochemical defect(s) that might be responsible for the diminished beta-adrenergic receptor responsiveness in the myocytes that survive in the infarcted heart.


RESULTS
We compared components of the beta-adrenergic receptor signaling pathway in membranes prepared from the EBZ of the 5-day infarcted heart and a remote, noninfarcted region (RZ) of the same ventricle as well as the corresponding regions of noninfarcted ventricles. Defects in multiple components of the beta-adrenergic receptor complex were confined to the EBZ of the 5-day infarcted heart. These include a decrease in beta-adrenergic receptor density; diminished basal, guanine nucleotide-, isoproterenol-, forskolin-, and manganese-dependent adenylyl cyclase activities; an increase in the EC50 for isoproterenol-dependent activation of adenylyl cyclase; a diminished level of the alpha-subunit of the Gs protein. and an elevated level of the alpha-subunit of the Gi protein.


CONCLUSIONS
Defects in multiple components of the membrane beta-adrenergic receptor complex were identified in the EBZ of the 5-day infarcted canine heart. This constellation of abnormalities would be predicted to impair functional beta-adrenergic responsiveness and contribute to the defect in isoproterenol-dependent stimulation of the L-type calcium current in myocytes isolated from this tissue.
Steinberg
S F
SF
Department of Medicine, Columbia University, New York, NY, USA.
Zhang
H
H
Pak
E
E
Pagnotta
G
G
Boyden
P A
PA
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D004285:Dogs; D005260:Female; D019204:GTP-Binding Proteins / Q000378:metabolism; D015151:Immunoblotting; D020120:Iodocyanopindolol; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009203:Myocardial Infarction / Q000378:metabolism / Q000503:physiopathology*; D009206:Myocardium / Q000378:metabolism; D010496:Pericardium / Q000294:innervation* / Q000378:metabolism; D010869:Pindolol / Q000031:analogs & derivatives; D011943:Receptors, Adrenergic, beta / Q000032:analysis / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors
D011943:Receptors, Adrenergic, beta; D020120:Iodocyanopindolol; D010869:Pindolol; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D007545:Isoproterenol