This Article Full Text Full Text (PDF) A correction has been published Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Abbey, S. E. Articles by Potter, L. R. Search for Related Content PubMed PubMed Citation Articles by Abbey, S. E. Articles by Potter, L. R.

Lysophosphatidic Acid Inhibits C-Type Natriuretic Peptide Activation of Guanylyl Cyclase-B

Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, Minnesota 55455

Address all correspondence and requests for reprints to: Lincoln R. Potter, Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, 6-155 Jackson, 321 Church Street SE, Minneapolis, Minnesota 55455. E-mail: potter{at}umn.edu.

C-type natriuretic peptide (CNP), found in endothelial cells, chondrocytes, and neurons, binds its cognate transmembrane receptor, natriuretic peptide receptor-B (NPR-B/GC-B), and stimulates the synthesis of the intracellular signaling molecule, cGMP. The known physiologic consequences of this binding event are vasorelaxation, inhibition of cell proliferation, and the stimulation of long bone growth. Here we report that 10% fetal bovine serum markedly reduced CNP-dependent cGMP elevations in NIH3T3 fibroblast. The purified serum components platelet-derived growth factor and lysophosphatidic acid (LPA) mimicked the effect of serum on CNP-dependent cGMP elevations, but the latter factor resulted in the most dramatic reductions. The LPA-dependent inhibition was rapid and dose dependent, having t_1/2 and IC₅₀ values of approximately 5 min and 3.0 µM LPA, respectively. The decreased cGMP concentrations resulted from reduced CNP-dependent NPR-B guanylyl cyclase activity that did not require losses in receptor protein or activation of protein kinase C, indicating a previously undescribed desensitization pathway. These data suggest that NPR-B is repressed by LPA and that one mechanism by which LPA exerts its effects is through the heterologous desensitization of the CNP/NPR-B/cGMP pathway. We hypothesize that cross-talk between the LPA and CNP signaling pathway maximizes the response of fibroblasts in the wound-healing process.

This article has been cited by other articles:

				L. K. Antos and L. R. Potter Adenine nucleotides decrease the apparent Km of endogenous natriuretic peptide receptors for GTP Am J Physiol Endocrinol Metab, December 1, 2007; 293(6): E1756 - E1763. [Abstract] [Full Text] [PDF]

				D. Muller, L. Cortes-Dericks, L. T. Budnik, B. Brunswig-Spickenheier, M. Pancratius, R. C. Speth, A. K. Mukhopadhyay, and R. Middendorff Homologous and Lysophosphatidic Acid-Induced Desensitization of the Atrial Natriuretic Peptide Receptor, Guanylyl Cyclase-A, in MA-10 Leydig Cells Endocrinology, June 1, 2006; 147(6): 2974 - 2985. [Abstract] [Full Text] [PDF]

				L. R. Potter, S. Abbey-Hosch, and D. M. Dickey Natriuretic Peptides, Their Receptors, and Cyclic Guanosine Monophosphate-Dependent Signaling Functions Endocr. Rev., February 1, 2006; 27(1): 47 - 72. [Abstract] [Full Text] [PDF]

				R. Potthast, S. E. Abbey-Hosch, L. K. Antos, J. S. Marchant, M. Kuhn, and L. R. Potter Calcium-dependent Dephosphorylation Mediates the Hyperosmotic and Lysophosphatidic Acid-dependent Inhibition of Natriuretic Peptide Receptor-B/Guanylyl Cyclase-B J. Biol. Chem., November 19, 2004; 279(47): 48513 - 48519. [Abstract] [Full Text] [PDF]

				P. Fidzinski, M. Salvador-Silva, L. Choritz, J. Geibel, and M. Coca-Prados Inhibition of NHE-1 Na+/H+ exchanger by natriuretic peptides in ocular nonpigmented ciliary epithelium Am J Physiol Cell Physiol, September 1, 2004; 287(3): C655 - C663. [Abstract] [Full Text] [PDF]

				T. Tokudome, T. Horio, T. Soeki, K. Mori, I. Kishimoto, S.-i. Suga, F. Yoshihara, Y. Kawano, M. Kohno, and K. Kangawa Inhibitory Effect of C-Type Natriuretic Peptide (CNP) on Cultured Cardiac Myocyte Hypertrophy: Interference between CNP and Endothelin-1 Signaling Pathways Endocrinology, May 1, 2004; 145(5): 2131 - 2140. [Abstract] [Full Text] [PDF]

				S. E. Abbey-Hosch, A. N. Cody, and L. R. Potter Sphingosine-1-Phosphate Inhibits C-Type Natriuretic Peptide Activation of Guanylyl Cyclase B (GC-B/NPR-B) Hypertension, May 1, 2004; 43(5): 1103 - 1109. [Abstract] [Full Text] [PDF]

				N. Tamura and D. L. Garbers Regulation of the Guanylyl Cyclase-B Receptor by Alternative Splicing J. Biol. Chem., December 5, 2003; 278(49): 48880 - 48889. [Abstract] [Full Text] [PDF]