Medical Journal of the Islamic Republic Of Iran
مجله پزشکی جمهوری اسلامی ایران
Med J Islam Repub Iran
Medical Sciences
http://mjiri.iums.ac.ir
2
journal2
1016-1430
2251-6840
8
10.18869/mjiri
14
8888
13
en
jalali
1383
2
1
gregorian
2004
5
1
18
1
online
1
fulltext
en
ANTICALMODULIN DRUGS DUE TO THE NET EFFECTS CANNOT ANTAGONIZE DIBUTYRYL-CAMP-MEDIATED SUPPRESSION OF DE NOVO SYNTHESIZED LIPID SECRETION IN BOTH CULTURED MCARDLE CELLS AND RAT HEPATOCYTES
Pediatric
Pediatric
Original Research: Basic Science in Medicine
Original Research: Basic Science in Medicine
The effects and interaction between cAMP-analogue dibutyryl-cAMP and
calmodulin antagonists were investigated on de novo synthesis and secretion of lipids in
cultures of hepatoma McArdle-RH7777 cells and normal rat hepatocytes. Dibutyryl cAMP caused a significant decrease in the secretion of de novo synthesized
triacyl [3H] glycerol in both cultures of McArdle cells and rat hepatocytes. The inhibitory
effect of dibutyryl-cAMP was concentration-dependent and appeared at the lowest
concentration examined, 5 µM. Dibutyryl-cAMP at a concentration of 50 11M suppressed
secretion of triacylglycerol by approximately 38% (p<0.05) and secretion of
phosphatidylcholine by 30% (p<0.05). Dibutyryl-cAMP did not affect the synthesis of
triacylglycerol and phosphatidylcholine, except at the highest concentration tested,
500 µM, where both triacylgJycerol and phosphatidylcholine synthesis were suppressed significantly.
Anticalmodulin W-7 also inhibited secretion of newly made triacylglycerol in a
concentration-dependent manner in both cultures of McArdle cells and rat hepatocytes.
W-7 at a concentration of 20 µM suppressed triacylglycerol secretion by about
37% (p<0.05), while the secretion of phosphatidylcholine and synthesis o f
triacylglycerol and phosphatidylcholine were not affected, unless at more than 20
µM concentration, at which both triacylglycerol and phosphatidylcholine synthesis were
decreased significantly.
The inhibitory effect elicited by dibutylyl-cAMP (100 µM) was not abolished in
the presence of calmodulin antagonists, W-7 (20 µM), trifluo perazine (20 µM) and
chlorpromazine (20 µM). The simultaneous effects of dibutyryl-cAMP and e ither
calmodulin antagonists were not additive or synergistic. None of the calmodulin antagonists
affected the cellular content of de novo synthesized triacylglycerol and p hosphatidy1choline
significantly. Neither dibutyryl-cAMP nor any calmodulin antagonist or
their combination did affect the overall rate of de novo synthesis of triacylglycerol and
phosphatidylcholine. All calmodulin antagonists examined alone also had a net significant
inhibitory effect on the secretion of newly made triacylglycerol. The results presented
here suggest that calmodulin antagonists have net direct effects and hence could
not overcome dibutyryl-cAMP-induced suppressive effects on the secretion of newly
made triacylglycerol. The cell types, normal hepatocytes relative to hepatomas, did not
influence the results.
Calmodulin, Cyclic AMP, Hepatocyte, PhosphatidyJcholine, McArdle cells, TriacygyceroJ and VLDL.
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http://mjiri.iums.ac.ir/browse.php?a_code=A-10-298-113&slc_lang=en&sid=1
MEHDI
RASOULI
mehdi2rasouli@yahoo.com.
20031947532846003639
20031947532846003639
Yes
University of Sari
RICHARD
LEHNER
richard.lehner@ualberta.ca
20031947532846003640
20031947532846003640
No
From the Department of Pediatrics alld Cell Biologv, CIHR Group on MoleclIlar and Cell Biology, of Lipids, University of Alberta, Edmonton, Canada, T6G 2S2