Decreases in ANP secretion by lysophosphatidylcholine through protein kinase C.
Lysophosphatidylcholine (LPC) is an endogenous phospholipid released from the cell membrane during ischemia, and it has potent, local effects on cardiac tissues. LPC has been implicated in arrhythmogenesis during ischemia by increasing intracellular Ca2+. However, it is not known whether LPC influences atrial release of atrial natriuretic peptide (ANP). The aim of this study was to investigate the effect of LPC on ANP secretion from isolated, perfused, beating rat atria. LPC (10 and 30 micromol/L) caused decreases in ANP secretion in a dose-dependent manner, with slight increases in intra-atrial pressure and extracellular fluid (ECF) translocation. Therefore, the ANP secretion in terms of ECF translocation was markedly decreased by LPC. The order of the suppressive effect of ANP release was stearoyl-LPC>LPC>myristoyl-LPC=lauroyl-LPC. Staurosporine and wortmannin significantly attenuated suppression of the ANP release and an increase in intra-atrial pressure by LPC. High extracellular Mg2+ also attenuated the LPC-induced suppression of ANP release. However, other protein kinase C inhibitors such as chelerythrine, GF 109203X, and tamoxifen citrate did not affect LPC-induced suppression of ANP release. In single atrial myocytes, LPC caused increases in intracellular Ca2+ in a dose-dependent manner. The order of an increase in intracellular Ca2+ by LPC was stearoyl-LPC>LPC>myristoyl-LPC=lauroyl-LPC. An increase in intracellular Ca2+ by LPC was attenuated by staurosporine. These results suggest that LPC-induced suppression of ANP release through protein kinase C/Ca2+ and phosphoinositol-3-kinase might in part play an important role in the development of hypertension.
Han
Jeong Hee
JH
Department of Physiology, Institute for Medical Sciences, Chonbuk National University Medical School, Jeonju 561-180, Korea.
Cao
Chunhua
C
Kim
Sung Zoo
SZ
Cho
Kyung Woo
KW
Kim
Suhn Hee
SH
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism*; D001692:Biological Transport; D002118:Calcium / Q000378:metabolism; D046508:Culture Techniques; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005110:Extracellular Space / Q000378:metabolism; D006325:Heart Atria / Q000166:cytology / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D008244:Lysophosphatidylcholines / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D009320:Atrial Natriuretic Factor; D002118:Calcium; D004791:Enzyme Inhibitors; D008244:Lysophosphatidylcholines; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011493:Protein Kinase C