Decreases in ANP secretion by lysophosphatidylcholine through protein kinase C.

Abstract

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.

• Authors: Jeong Hee Han, Chunhua Cao, Sung Zoo Kim, Kyung Woo Cho, Suhn Hee Kim
• Journal: Hypertension (Dallas, Tex. : 1979) (Hypertension) Vol. 41 Issue 6 Pg. 1380-5 (Jun 2003) ISSN: 1524-4563 [Electronic] United States
• PMID: 12719444 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Enzyme Inhibitors
• Lysophosphatidylcholines
• Phosphoinositide-3 Kinase Inhibitors
• Atrial Natriuretic Factor
• Protein Kinase C
• Calcium

Topics

• Animals
• Atrial Natriuretic Factor (metabolism)
• Biological Transport
• Calcium (metabolism)
• Culture Techniques
• Enzyme Inhibitors (pharmacology)
• Extracellular Space (metabolism)
• Heart Atria (cytology, drug effects, enzymology, metabolism)
• Lysophosphatidylcholines (antagonists & inhibitors, pharmacology)
• Male
• Myocytes, Cardiac (drug effects, metabolism)
• Phosphatidylinositol 3-Kinases (physiology)
• Phosphoinositide-3 Kinase Inhibitors
• Protein Kinase C (antagonists & inhibitors, physiology)
• Rats
• Rats, Sprague-Dawley