AJP - Lung Cellular and Molecular Physiology, Vol 257, Issue 4 253-L258, Copyright © 1989 by American Physiological Society

ARTICLES

Translocation of protein kinase C is associated with inhibition of 5-HT uptake by cultured endothelial cells

C. L. Myers, J. S. Lazo and B. R. Pitt
Department of Anesthesiology, Yale University School of Medicine, New Haven, Connecticut 06510.

Acute exposure (30 min-1 h) of bovine pulmonary artery endothelial cells in culture (BPAEC) to phorbol myristate acetate (PMA 10(-10)-10(-6) M) resulted in concentration-dependent decrement in serotonin (5-HT) uptake. Neither cell viability (trypan blue exclusion or release of deoxyglucose) nor activity of another plasma membrane function, angiotensin-converting enzyme activity, were affected. A decrease in 5-HT uptake was also noted with phorbol 12,13 dibutyrate and mezerein, but not with 4-alpha-phorbol 12,13 didecanoate, which does not stimulate protein kinase C (PKC). Inhibition of 5-HT uptake by PMA (160 nM) was reversed in a concentration-dependent manner by pretreatment of cells with the PKC inhibitor staurosporine (3-100 nM). BPAEC were treated with PMA (160 nM) for 1 h, and activities of PKC in cytosolic and membrane compartments were determined. PMA did not significantly affect total cellular PKC activity but resulted in a translocation of activity from cytosol to membrane (control membrane activity 67 +/- 4%; PMA-treated membrane activity 97 +/- 1% of total cellular PKC). Thus we propose that translocation of PKC from cytosol to membrane results in inhibition of 5-HT uptake by BPAEC.

This article has been cited by other articles:

				G. M. Daniels and S. G. Amara Regulated Trafficking of the Human Dopamine Transporter. CLATHRIN-MEDIATED INTERNALIZATION AND LYSOSOMAL DEGRADATION IN RESPONSE TO PHORBOL ESTERS J. Biol. Chem., December 10, 1999; 274(50): 35794 - 35801. [Abstract] [Full Text] [PDF]

				G. Pineyro and P. Blier Autoregulation of Serotonin Neurons: Role in Antidepressant Drug Action Pharmacol. Rev., September 1, 1999; 51(3): 533 - 591. [Abstract] [Full Text] [PDF]

				S. Ramamoorthy, E. Giovanetti, Y. Qian, and R. D. Blakely Phosphorylation and Regulation of Antidepressant-sensitive Serotonin Transporters J. Biol. Chem., January 23, 1998; 273(4): 2458 - 2466. [Abstract] [Full Text] [PDF]

				B. R. Pitt, M. Schwarz, E. S. Woo, E. Yee, K. Wasserloos, S. Tran, W. Weng, R. J. Mannix, S. A. Watkins, Y. Y. Tyurina, et al. Overexpression of metallothionein decreases sensitivity of pulmonary endothelial cells to oxidant injury Am J Physiol Lung Cell Mol Physiol, October 1, 1997; 273(4): L856 - L865. [Abstract] [Full Text] [PDF]

				D. E. Krantz, D. Peter, Y. Liu, and R. H. Edwards Phosphorylation of a Vesicular Monoamine Transporter by Casein Kinase II J. Biol. Chem., March 7, 1997; 272(10): 6752 - 6759. [Abstract] [Full Text] [PDF]

				Y. Qian, A. Galli, S. Ramamoorthy, S. Risso, L. J. DeFelice, and R. D. Blakely Protein Kinase C Activation Regulates Human Serotonin Transporters in HEK-293 Cells via Altered Cell Surface Expression J. Neurosci., January 1, 1997; 17(1): 45 - 57. [Abstract] [Full Text] [PDF]