Biology Reference
In-Depth Information
cGMP-hydrolytic activity
cAMP-hydrolytic activity
140
Total
Soluble
250
Total
PDE1
120
PDE1
Total
PDE1
Total
200
100
PDE1
150
80
60
100
PDE3
40
PDE3
50
PDE3
PDE3
20
0
0
Normal
Failing
Normal
Failing
30
Total
Particulate
Total
80
Total
Total
25
60
PDE3
20
PDE3
PDE1
PDE1
15
40
10
PDE1
PDE3
PDE1
PDE3
20
5
0
0
Normal
Failing
Normal
Failing
Fig. 1 cAMP- and cGMP-hydrolytic activity in soluble and particulate fractions of normal and
failing human left ventricular myocardium. Assays were performed at 0.1
m
M cAMP
PDE3A
DNA
?
mRNA
AUG: 2
AUG: 4
7
PDE3A3
PKA/PKC/PKB
CCR
P1
P2 P3
PKA/PKC/PKB
PDE3A1
NHR1
NHR2
CCR
P2 P3
PDE3A2
Catalytic
domain
Membrane-
insertion
domain
Protein-
binding
domain
NHR2
CCR
Fig. 2 PDE3A isoforms in human myocardium. Two messages appear to be generated by
transcription from alternate sites in the first exon of
PDE3A
. The longer message appears to be
translated from its second AUG to yield PDE3A1; the shorter message appears to be translated
from downstream AUGs to yield PDE3A2 and PDE3A3
and are identical with respect
to catalytic activity and inhibitor sensitivity
(Hambleton et al.
2005
).
There are conflicting reports regarding the level of PDE3 activity in normal and
failing human myocardium. In one study, the expression of PDE3 was reported
to be decreased in patients with dilated cardiomyopathy (Ding et al.
2005a
).
