Cardiomyopathic Hamster Heart Cells - Phospholipid Metabolism in
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1015
Phospholipid Metabolism in
Cardiomyopathic Hamster Heart Cells
Hideaki Kawaguchi, Mikako Shoki, Hitoshi Sano, Toshiyuki Kudo,
Hirofumi Sawa, Hiroshi Okamoto, Yoshihito Sakata, and Hisakazu Yasuda
We demonstrated that the activities of phosphatidylinositide-specific phospholipase C, inositol
1,4,5-trisphosphate (IP3) kinase, and 1P3 phosphatase were enhanced in cardiomyopathic
hamster hearts (BIO 14.6 and BIO 53.58) in comparison to control hamsters (Flb). Release of
both arachidonic acid and prostacyclin was markedly enhanced by norepinephrine in the
cardiomyopathic hamsters. Phospholipase C in heart has high substrate specificity to phos-
phatidylinositol. 1P3 production was markedly enhanced in the cardiomyopathic hamsters. We
also determined the intracellular calcium concentration, which was higher in BIO 53.58
hamsters than in BIO 14.6 hamsters at 5-20 weeks of age. There was no significant difference
in the intracellular calcium level between Flb and BIO 14.6 hamsters at 5 weeks of age. These
results suggest that phosphatidylinositol turnover stimulated by norepinephrine may produce
high intracellular calcium levels in both BIO 14.6 and BIO 53.58 myocytes. In addition, in BIO
53.58 hamsters, some mechanism such as the sarcoplasmic reticulum, which controls the
intracellular calcium level, may deteriorate in function. We concluded from these results that
a prolonged high intracellular calcium level may lead to the death of BIO 53.58 myocytes.
(Circulation Research 1991;69:1015-1021)
Syrian cardiomyopathic hamsters (BIO 14.6 and trisphosphate (IP3) and sn-1,2-diacylglycerol
BIO 53.58) display hereditary abnormalities (DAG).9,10 DAG stimulates membrane-bound phos-
of the cardiac and skeletal muscles that are pholipid-dependent, Ca2+-dependent protein kinase
inherited as an autosomal recessive trait.1 BIO 14.6 C," whereas 1P3 releases Ca21 from stores in the
cardiac involvement results in initial myocardial hy- endoplasmic reticulum.12"3 Removal of 1P3 occurs by
pertrophy followed by cardiac dilation and death two different pathways: hydrolysis to inositol 1,4-
from congestive heart failure.2 Calcium overload of bisphosphate (IP2) and phosphorylation to inositol
myocytes has been implicated in the etiology of these 1,3,4,5 -tetrakisphosphate (IP4).14-19 1P4 subsequently
abnormalities, because calcium uptake by the myo- is dephosphorylated to 1,3,4-IP3, which is relatively
cardium is increased and calcium antagonists are inactive in releasing Ca21 when compared with the
effective in improving the manifestations of the dis- 1,4,5-IP3 isomer.20 The physiological significance of
ease. It is thought that the cardiomyopathic hamster this extra loop of the PI turnover pathway is unknown
provides a useful model of human cardiac diseases in any mammalian cell system, but in sea urchin eggs,
such as hypertrophic cardiomyopathy.3,4 1P4 has been shown to enhance Ca2' entry into the
The primary event in the mechanism of action of cell.21 However, this phenomenon has not been
many different hormones and neurotransmitters is shown to occur in cardiac myocytes. This phosphor-
the receptor-mediated stimulation of the breakdown ylation/dephosphorylation pathway generally is con-
of plasma membrane inositol phospholipids.5,6-8 This sidered an integral part of the PI turnover pathway.
so-called phosphatidylinositol (PI) turnover pathway We have suggested that this aspect of phospholipid
generates two second messengers: inositol 1,4,5- metabolism may have an important role in inducing
myocardial cell damage and cardiac myocyte hyper-
From the Department of Cardiovascular Medicine, Hokkaido trophy. Accordingly, this experiment investigated
University School of Medicine, Sapporo, Japan. polyphosphoinositide metabolism in the hearts of
Supported in part by a research grant for cardiomyopathy from dilated and hypertrophic cardiomyopathic hamsters.
the Ministry of Health and Welfare of Japan and grants-in-aid for
scientific research from the Ministry of Education, Science and
Culture of Japan, 01870041, 02404042, and 02454250. Materials and Methods
Address for correspondence: Hideaki Kawaguchi, Department Experimental Protocol
of Cardiovascular Medicine, Hokkaido University School of Med-
icine, Sapporo 060 Japan. Experiments were carried out using male hyper-
Received November 1, 1990; accepted May 24, 1991. trophic cardiomyopathic hamsters (BIO 14.6) aged 5,
Downloaded from http://circres.ahajournals.org/ by guest on March 5, 20151016 Circulation Research Vol 69, No 4 October 1991
10, 20, and 30 weeks and age-matched male dilated Phospholipid hydrolysis stimulated by norepineph-
cardiomyopathic hamsters (BIO 53.58) (Bio Breed- rine also was determined in the presence of 1 ,uM
ers, Inc., Fitchburg, Mass.).4 Fib hamsters were used metoprolol. Triplicate cultures of myocytes were
as controls, and each age group was composed of 10 biosynthetically labeled with 5 ,uCi methyl-
animals. The BIO 14.6 strain of cardiomyopathic [3H]choline, myo-[3H]inositol, or [3H]ethanolamine
golden Syrian hamsters develops the following char- (20, 78, and 30 Ci/mmol, respectively) (Radiochemi-
acteristic pathological changes: cardiac myolysis at cal Centre). The cells were incubated for 30 minutes
4-5 weeks of age, cardiac hypertrophy at approxi- at 37°C with the indicated norepinephrine concentra-
mately 20 weeks of age, cardiac dilation at approxi- tions. The radioactive materials in the cells and
mately 30-40 weeks of age, and congestive heart medium were extracted, and the combined extracts
failure at approximately 1 year of age.4 In contrast to were analyzed by thin-layer chromatography (solvent
BIO 14.6 hamsters, BIO 53.58 hamsters do not system: methanol/chloroform/acetic acid/water,
develop myolysis or hypertrophy before dilation. BIO 50:30:8:4, vol/vol) with authentic standards.
53.58 hamsters gradually develop cardiac dilation at Phospholipase C Activity
approximately 4-20 weeks of age, which is accompa- For the determination of the cellular phospholi-
nied with diffuse cell death; they also have a signifi- pase C activity, cells (1 x 105) first were labeled with 5
cantly shorter life span and demonstrate reduced ,Ci myo-[3H]inositol, [3H]choline chloride, or [3HIeth-
cardiac function at an earlier age than do the BIO anolamine. Labeling was performed for 24 hours in
14.6 hamsters.34 Therefore, the BIO 53.58 hamster phosphate buffer with 0.3% fetal calf serum, after
provides a model of cardiac dilation that contrasts which cells were washed three times with phosphate
with the hypertrophic model of the BIO 14.6 strain. buffer. Cells then were incubated with the indicated
The Flb strain is an Fl hybrid of strains BIO 1.5 and concentrations of norepinephrine, 5 mM 2,3-diphos-
BIO 87.2. phoglyceric acid (2,3-DPG; this concentration inhib-
The left ventricle was excised from each heart, and ited the dephosphorylation of 1P3 and 1P4 by 98%),
the blood was carefully washed out. and 10 mM LiCl for the indicated periods in the
presence of 1 ,uM metoprolol; the incubation was
Cell Preparation terminated with chloroform/methanol (2:1, vol/
Cardiac myocytes from BIO 14.6, BIO 53.58, and vol).30 Phospholipids were fractionated by thin-layer
Flb hamsters were prepared in phosphate buffer chromatography with a chloroform/methanol/acetic
according to a previously reported method22 and then acid/water solvent system (50:30:8:4, vol/vol).31 For
cultured in Ham's F-10 medium with 10% fetal calf the separation of polyinositol phosphatides, the
serum until use. Freshly prepared cells were main- aqueous phase was applied to an AG1 x8 column in
tained at 37°C in a humidified 5% C02-95% air format form (100-200 mesh; Bio-Rad Laboratories,
atmosphere.23 Cells then were subcultured for assay Richmond, Calif.), and inositol phosphates were
in 35-mm dishes at 3 X 105 cells/dish in 1 ml phos- separated by an ammonium gradient system (0.2-1.2
phate buffer containing 1 mM CaCl2 and were used M) plus 0.1 M formic acid.32'33 For a more detailed
within 2 hours.24 analysis, including the separation of inositol phos-
phate isomers, samples were filtered and separated
Phospholipase A2 Activity by high-performance liquid chromatography (Partisil
Triplicate cultures of lx 105 cells were plated in 10 SAX anion-exchange column with a guard col-
35-mm Falcon plastic dishes in 2 ml Krebs-Henseleit umn, Whatman Inc., Clifton, N.J.) using a gradient of
solution and HEPES buffer (pH 7.4) containing 0.3% ammonium formate and phosphate.1617 The release
fetal bovine serum and 1 ,uCi [3H]arachidonic acid of 1P3 also was determined with an 1P3-binding
(135 Ci/mol, Radiochemical Centre, Amersham, UK) protein system (myoinositol-1,4,5-trisphosphate as-
and were cultured for 24 hours.25 The incorporation say system, Amersham, UK).34 For the determination
of [3H]arachidonic acid into cardiac myocytes was of DAG release,27 cells first were labeled with [3H]ara-
22±6%. The cells on the dishes were washed three chidonic acid (1 uCi/dish) and then incubated with
times with 2 ml of the medium and then incubated norepinephrine as described above. For the determi-
with norepinephrine at 37°C for up to 60 minutes in nation of monoacylglyceride (MG) release, triplicate
the presence of 1 ,uM metoprolol (Japan CIBA- cultures of cells were prelabeled with [3H]glycerol (3
GEIGY, Osaka, Japan) to exclude the effect of ,uCi/dish) for 24 hours at 37°C and then were incu-
a1-adrenergic receptor stimulation. The lipids re- bated with 1 ,M norepinephrine for the indicated
leased into the medium from cells were extracted periods at 37°C as described previously.27 After stim-
with 2 ml ethyl acetate and analyzed by thin-layer ulation by norepinephrine in the presence of 1 ,uM
chromatography.26-28 Further identification of the metoprolol, 1P3 kinase and inositol 5-phosphatase
reaction products was done using high-performance activities were determined in cells permeabilized
liquid chromatography.29 The retention times of with saponin (10 ,ug/ml, a concentration that did not
6-ketoprostaglandin F,a, thromboxane B2, pros- affect either enzyme activity).14 Cells were preincu-
taglandin F2, and prostaglandin E2 were 3, 5, 7, and bated with 1 ,uM norepinephrine for 2 minutes, then
12 minutes, respectively. saponin and the substrate (IP3 or 1P4) were added
Downloaded from http://circres.ahajournals.org/ by guest on March 5, 2015Kawaguchi et al Increased Phospholipid Metabolism in Cardiomyopathy 1017
TABLE 1. Heart Weight, Release of 6-Ketoprostaglandin F1,, and Arachidonic Acid, and Phospholipid Hydrolysis
Heart wt/body wt
Hamster (mg/g) Release of Phospholipid hydrolysis Release of
strain 5 weeks 20 weeks 6-Keto-PGF1a AA PC PI PE LysoPC LysoPI LysoPE DAG MG
BIO 14.6 3.9+0.2* 3.6±0.1 1.3±0.1t 15±1t 99 68±11t 99 1 0 0 9.5±1t 3t
BIO 53.58 2.7±0.2* 3.2±0.1t 1.4±0.1t 16±2t 99 62±4t 99 0 0 0 9.0± it 3±0.5t
Flb 3.4±0.4 3.6±0.2 0.4±0.1 5±2 99 87±3 99 1 1 0 3.2±1 0.8
Values are mean±SEM. Heart rate/body weight ratio shown for hamsters aged 5 and 20 weeks. Effect of 1 M norepinephrine shown on
release of 6-ketoprostaglandin F,,, (6-keto-PGFia) and arachidonic acid (AA); total 6-keto-PGFia release shown as percentage of total
incorporated [3H]AA. Phospholipid hydrolysis stimulated by norepinephrine shown as percentage ottincorporated radioactivity migrating
with phosphatidylcholine (PC), phosphatidylinositol (PI), phosphatidylethanolamine (PE), lysoPC, lysoPI, and lysoPE. Effect of 1 M
norepinephrine shown on release of diacylglyceride (DAG) and monoacylglyceride (MG) from myocytes.
*p1018 Circulation Research Vol 69, No 4 October 1991
(A) (B) (A) (B)
tl)
9- x
x
a
CM
a 0
Db
aU60)* X
(U
co
0
CL
C')h.
Incubation Time (min) -Log[NEJ M
30 60
40 (C) 40- (D) Time(sec) Time(sec)
FIGURE 2. Effect of norepinephrine stimulation on inositol
30 30 monophosphate (IP; panel A) and inositol 1,4,5-trisphos-
phate (IP3; panel B) production in cardiomyopathic and Flb
' 20 20' hamsters aged 10 weeks, determined as described in "Materi-
als and Methods." A, BIO 14.6 hamsters; *, BIO 53.58
k k hamsters; o, Flb hamsters.
and BIO 53.58 hamsters (Figure 4, pKawaguchi et al Increased Phospholipid Metabolism in Cardiomyopathy 1019
4
._
0 0 300 7
0
Ir 3
E *t
CL E
'- 0 200 - *t *
02 0_.
E
0
1.. a
0.
CL
0
4)
CD
1001-
0
L
L.
5 10 20 30
a.
Time(sec) AGE(WEEKS)
FIGURE 4. Effects of norepinephrine on inositol 1,3,4,5- FIGURE 6. Effects of norepinephrine stimulation on inositol
tetrakisphosphate (IP4) release in cells of cardiomyopathic 1,4,5-trisphosphate (IP3) release in BIO 14.6 hamsters
and Flb hamsters aged 10 weeks, determined as described in (hatched bars), BIO 53.58 hamsters aged 5-30 weeks (cross-
"Materials and Methods." A, BIO 14.6 hamsters; *, BIO hatched bars), and Flb hamsters (open bars). Each activity
53.58 hamsters; o, Flb hamsters. was determined as described in "Materials and Methods" in
the presence of 1 MM metoprolol. *p1020 Circulation Research Vol 69, No 4 October 1991
levels of radioactive choline and ethanolamine in the Recently, it was reported that diminished f-adren-
medium showed only small changes, but an increase in ergic receptor responsiveness and cardiac dilation in
the level of inositol was observed. These results sug- heart of BIO 53.58 hamsters are associated with a
gested that norepinephrine stimulated phospholipase functional abnormality of the guanine nucleotide-bind-
C, which has substrate specificity toward PI. After the ing regulatory protein that stimulates adenylyl cyclase
activation of phospholipase C, some of the arachi- (GS).45 In contrast, the present results show that a1-
donic acid released was converted to prostacyclin. adrenergic receptor stimulation may cause intracellular
We tried to characterize the phospholipase C calcium overload because of deterioration of sarcoplas-
activity stimulated by a1-adrenergic receptor stimu- mic reticulum function in BIO 53.58 hamsters.
lation. It stimulated phosphatidylinositol 4,5 -
bisphosphate-specific phospholipase C activity and References
released 1P3. Neomycin suppressed the enhancement 1. Bajusz E: Hereditary cardiomyopathy: A new disease model.
of phospholipase C activity by a1-adrenergic receptor Am Heart J 1969;77:686-696
stimulation, which stimulated 1P3 release. 2. Strobeck JE, Factor SM, Bhan A, Sole M, Liew CC, Fein F,
The metabolism of phosphatidylinositol 4,5 - Sonnenblick EH: Hereditary and acquired cardiomyopathies
bisphosphate stimulated by a1-adrenergic receptor in experimental animals: Mechanical, biochemical, and struc-
stimulation has been studied extensively in the heart, tural features. Ann N YAcad Sci 1979;317:59-88
3. Homburger F, Baker JR, Nixon CW, Whitney R: Primary
and the results demonstrate that 1,4,5 -1P3 and generalized polymyopathy and cardiac necrosis in an inbred
1,3,4,5-IP4 are the immediate routes of metabolism.38 line of Syrian hamsters. Med Exp 1962;6:339-345
It is known that 1,4,5 -1P3 mobilizes intracellular 4. Bajuz E, Baker JR, Nixon CW, Homburger F: Spontaneous
Ca2+, but whether this also occurs in the heart is a hereditary myocardial degeneration and congestive heart fail-
matter of dispute.39,40 It also is reported that 1,3,4,5- ure in a strain of Syrian hamsters. Ann N Y Acad Sci
1969;156:105-129
IP4 enhances Ca2+ entry into some cells21 and poten- 5. Brown JH, Buxton IL, Brunton LL: a1-Adrenergic and mus-
tiates the Ca2+ mobilizing effect of 1,4,5 -IP3.41 There- carinic cholinergic stimulation of phosphoinositide hydrolysis
fore, 1,4,5-IP3 and 1,3,4,5-IP4 may have an important in adult rat cardiomyocytes. Circ Res 1985;57:532-537
role in controlling Ca2+ levels in response to hor- 6. Fasolato C, Pandiella A, Meldolesi J, Pozzan T: Generation of
monal stimulation,38,42 but it remains to be shown inositol phosphate, cytosolic Ca2+, and ionic fluxes in PC12
cells treated with bradykinin. J Biol Chem 1988;263:
that this phenomenon occurs in cardiac myocytes. In 17350-17359
our experiment, the accumulations of IP, 1P3, and 1P4 7. Baker KM, Singer HA: Identification and characterization of
after stimulation with norepinephrine were signifi- guinea pig angiotensin II ventricular and atrial receptors:
cantly enhanced in cardiac myocytes of cardiomyo- Coupling to inositol phosphate production. Circ Res 1988;62:
896-904
pathic hamsters. These results suggest the possibility 8. Dubyak GR, Cowen DS, Meuller LM: Activation of inositol
that the enhanced phosphatidylinositol 4,5-bisphos- phospholipid breakdown in HL60 cells by P2-purinergic
phate-IP3-Ca2+ pathways and the DAG-protein ki- receptors for extracellular ATP. J Biol Chem 1988;263:
nase C pathway may increase protein synthesis in the 18108-18117
BIO 14.6 heart. However, this hypothesis does not 9. Berridge MJ: Inositol trisphosphate and diacylglycerol as
second messengers. Biochem J 1984;220:345-360
explain how myocardial cell damage occurs in BIO 10. Williamson JR, Cooper RH, Joseph NE, Thomas AP: Inositol
53.58 hamsters. In both animals, the PI metabolism trisphosphate and diacylglycerol as intracellular second mes-
and the polyphosphoinositide metabolism are en- sengers in liver. Am J Physiol 1985;248:C203-C216
hanced, but one develops cardiac hypertrophy and 11. Nisizuka Y: Phospholipid degradation and signal translation
for protein phosphorylation. Trends Biochem Sci 1983;8:13-16
the other develops cardiac dilation. This difference 12. Putney JW: Formation and actions of calcium-mobilizing
may be partly explained by the cytosolic Ca21 con- messenger, inositol 1,4,5-trisphosphate.Am JPhysiol 1987;252:
centration shown in Figure 7. The cytosolic Ca2+ G149-G157
concentration was quite high in BIO 53.58 hamsters 13. Ehrlich BE, Watras J: Inositol 1,4,5-trisphosphate activates a
aged 4-30 weeks, but in BIO 14.6 hamsters, it channel from smooth muscle sarcoplasmic reticulum. Nature
1988;336:583-586
increased at 30 weeks of age. As mentioned above, an 14. Tennes KA, McKinney JS, Putney JW: Metabolism of inositol
increase in the PI response may raise the cytosolic 1,4,5-trisphosphate in guinea pig hepatocytes. Biochem J 1987;
Ca2+ level, but in BIO 14.6 hamsters aged 4-20 242:797-802
weeks, it was still lower than in BIO 53.58 hamsters. 15. Irvine RF, Letcher AJ, Heslop JP, Berridge MJ: The inositol
These results suggest that the intracellular calcium tris/tetrakisphosphate pathway-demonstration of Ins(1,4,5)P3
3-kinase activity in animal tissues. Nature 1986;320:631-634
handling is seriously disturbed from a very young age 16. Batty IR, Nahorski SR, Irvine RF: Rapid formation of inositol
in BIO 53.58 hamsters. On the other hand, it appears 1,3,4,5-tetrakisphosphate following muscarinic receptor stim-
to be well-preserved in the early stages of hyper- ulation of rat cerebral cortical slices. Biochem J 1985;232:
trophic cardiomyopathy in BIO 14.6 hamsters. Our 211-215
17. Hawkins PT, Stephens L, Downes CP: Rapid formation of
results are supported by a previous report43 that inositol 1,3,4,5-tetrakisphosphate and inositol 1,3,5-
described that calcium uptake into sarcoplasmic re- trisphosphate in rat parotid glands may both result indirectly
ticulum decreased in BIO 53.58 hamsters compared from receptor-stimulated release of inositol 1,4,5-trisphos-
with BIO 14.6 and Flb hamsters. It also was reported phate from phosphatidylinositol 4,5-bisphosphate. Biochem J
previously" that calcium uptake into the sarcoplas- 1986;238:507-516
18. Morris AJ, Murray KJ, England PJ, Downes CP: Partial
mic reticulum of transplanted hearts with dilated purification and some properties of rat brain inositol 1,4,5-
cardiomyopathy is markedly reduced. trisphosphate 3-kinase. Biochem J 1988;251:157-163
Downloaded from http://circres.ahajournals.org/ by guest on March 5, 2015Kawaguchi et al Increased Phospholipid Metabolism in Cardiomyopathy 1021
19. Johanson RA, Hansen CA, Williamson JR: Purification of 35. Kawaguchi H, lizuka K, Takahashi H, Yasuda H: Inositol
D-myo-inositol 1,4,5-trisphosphate 3-kinase from rat brain. J triphosphate kinase activity in hypertrophied rat heart. Bio-
Biol Chem 1988;263:7465-7471 chem Med Metab Biol 1990;44:42-50
20. Bradford PG, Irvine RF: Specific site for [3H]inositol 36. Wallenstein S, Zucker CL, Fleiss J: Some statistical methods
(1,3,4,5)tetrakisphosphate on membrane of HL-60 cells. Bio- useful in circulation research. Circ Res 1980;47:1-9
chem Biophys Res Commun 1987;149:680-685 37. Habenicht AJR, Glomset JA, King WC, Nist C, Mitchell CD,
21. Irvine RF, Moor RM: Micro-injection of inositol 1,3,4,5- Ross R: Early change in phosphatidylinositol and arachidonic
tetrakisphosphate activities in sea urchin eggs by a mechanism acid metabolism in quiescent Swiss 3T3 cells stimulated by
dependent on external Ca2+. Biochem J 1986;240:917-920 platelet-derived growth factors. J Biol Chem 1981;256:
22. Glick MR, Burns AH, Reddy WJ: Dispersion and isolation of 12329-12335
beating cells from adult rat heart. Anal Biochem 1974;61: 38. Heathers GP, Corr PB, Rubin UJ: Transient accumulation of
32-42 inositol (1,3,4,5)-tetrakisphosphate in response to a1-adrener-
23. Kawaguchi H, Yasuda H: Effect of elastase on prostacyclin gic stimulation in adult cardiac myocytes. Biochem Biophys Res
synthesis in aortic smooth muscle cells. Biochim Biophys Acta Commun 1988;156:485-492
1986;878:42-48 39. Movsesian MA, Thomas AP, Selak M, Williamson JR: Inositol
24. Kawaguchi H, Sawa H, Yasuda H: Mechanism of increased trisphosphate does not release Ca2+ from permeabilized car-
angiotensin-converting enzyme activity stimulated by platelet- diac myocytes and sarcoplasmic reticulum. FEBS Lett 1985;
activating factor. Biochim Biophys Acta 1990;1052:503-508 185:328-332
25. Kawaguchi H, Yasuda H: Platelet-activating factor stimulates 40. Nosek TM, Williams MF, Zeigler ST, Godt RE: Inositol
prostaglandin synthesis in cultured cells. Hypertension 1986;8: trisphosphate enhances calcium release in skinned cardiac and
192-197 skeletal muscle. Am J Physiol 1986;250:C807-C811
26. Kawaguchi H, Yasuda H: Prostacyclin biosynthesis and phos- 41. Irvine RF, Moor RM: Inositol (1,3,4,5) tetrakisphosphate-in-
pholipase activity in hypoxic rat myocardium. Circ Res 1988; duced activation of sea urchin eggs requires the presence of
62:1175-1181 inositol trisphosphate. Biochem Biophys Res Commun 1987;
27. Kawaguchi H, Yasuda H: Effect of various plasminogen 146:284-290
activators on prostacyclin synthesis in cultured vascular cells. 42. Kohl C, Schmitz W, Scholz H, Scholz J, Toth M, Doring V,
Circ Res 1988;63:1029-1035 Kalmar P: Evidence for a1-adrenergic-mediated increase of
28. Kawaguchi H, Yasuda H: Effect of platelet-activating factor inositol trisphosphate in the human heart. J Cardiovasc Phar-
on arachidonic acid metabolism in renal epithelial cells. macol 1989;13:324-327
Biochim Biophys Acta 1986;875:525-534 43. Whitmer JT, Kumar P, Solaro RJ: Calcium transport proper-
29. Kawaguchi H, Okamoto H, Saito H, Yasuda H: Renal phos- ties of cardiac sarcoplasmic reticulum from cardiomyopathic
pholipase C and diglyceride lipase activity in spontaneously Syrian hamsters (BIO 53.58 and 14.6): Evidence for a quanti-
hypertensive rats. Hypertension 1987;10:100-106 tative defect in dilated myopathic hearts not evident in hyper-
30. Folch J, Lee W, Sloane-Stanley GH: A simple method for the trophic hearts. Circ Res 1988;62:81-85
isolation and characterization of total lipids from animal 44. Gwathmey JK, Copelas L, MacKinnon R, Schoen FJ, Feldman
tissues. J Biol Chem 1957;226:497-509 MD, Drossman W, Morgan JP: Abnormal intracellular cal-
31. Kawaguchi H, Yasuda H: Effect of elastase on phospholipase cium handling in myocardium from patients with end-stage
activity in aortic smooth muscle cells. Biochim Biophys Acta heart failure. Circ Res 1987;61:70-76
1988;958:450-459 45. Feldman AM, Tena RG, Kessler PD, Weisman HF, Schulman
32. Downes CP, Hawkins PT, Irvine RF: Inositol 1,3,4,5- SP, Blumenthal RS, Jackson DG, Van Dop C: Diminished
tetrakisphosphate and not phosphatidylinositol 3,4-bisphos- P-adrenergic receptor responsiveness and cardiac dilation in
phate is the probable precursor of inositol 1,3,4-trisphosphate hearts of myopathic Syrian hamsters (BIO 53.58) are associ-
in agonist-stimulated parotid gland. Biochem J 1986;238: ated with a functional abnormality of the G stimulatory
501-506 protein. Circulation 1990;81:1341-1352
33. Merritt JE, Taylor CW, Rubin RP, Putney JW: Isomers of
inositol trisphosphate in exocrine pancreas. Biochem J 1986;
238:825-829
34. Podzuweit T, Granz M, Muller A, Schaper W: Inositol (1,4,5)- KEY WoRDs * phosphatidylinositide-specific phospholipase C
trisphosphate levels in ischemic and reperfused pig myocar- inositol 1,4,5-trisphosphate * inositol trisphosphate kinase .
dium (abstract). J Mol Cell Cardiol 1989;21:S34 inositol trisphosphate phosphatase
Downloaded from http://circres.ahajournals.org/ by guest on March 5, 2015Phospholipid metabolism in cardiomyopathic hamster heart cells.
H Kawaguchi, M Shoki, H Sano, T Kudo, H Sawa, H Okamoto, Y Sakata and H Yasuda
Circ Res. 1991;69:1015-1021
doi: 10.1161/01.RES.69.4.1015
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