2171429

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1

Phorbol 12-myristate 13-acetate (PMA), a potent protein kinase C activator, caused down-regulation of receptors for platelet-activating factor (AGEPC) on the plasma membrane of rat Kupffer cells (40-50% reduction) but had a relatively minor effect on the binding affinity of the receptors for AGEPC (Kd = 0.30 nM vs 0.56 nM) when incubated with the cells for a short period of time (30-60 min). As a consequence, the AGEPC receptor-mediated arachidonic acid release was attenuated. The PMA-induced down-regulation of AGEPC receptors was concentration-dependent, specific, and transient (the maximal effect was observed at about 1 h and the level of specific [3H]AGEPC binding gradually returned to the control level within 8.5 h and even higher than the control level at 24 h after addition of PMA). Upon removing PMA from the culture medium, more than half of the lost receptors were replaced within 1 h at 37 degrees C and the recovery process appeared to be independent of protein synthesis. The ability of PMA to down-regulate the AGEPC receptors was lost in cells "down-regulated" for protein kinase C, suggesting that the receptor-regulatory effect of PMA is protein kinase C-dependent. Protein kinase C appeared to be involved in the AGEPC-induced arachidonic acid release since 1-(5-isoquinolinesulfonyl)-2-methyl-piperazine dihydrochloride, a protein kinase C inhibitor, attenuated the stimulatory effect of AGEPC in this system. In addition, AGEPC-induced [3H]arachidonic acid release was inhibited significantly in cells down-regulated for protein kinase C. The present study thus demonstrates that protein kinase C has dual actions in the regulation of AGEPC-mediated events, i.e., a positive forward action, regulating AGEPC-stimulated arachidonic acid release, and a negative action, which inactivates or down-regulates AGEPC receptors.

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MEDLINE

0003-9861

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188-97

pubmed-meshheading:2171429-Animals, pubmed-meshheading:2171429-Arachidonic Acid, pubmed-meshheading:2171429-Arachidonic Acids, pubmed-meshheading:2171429-Calcimycin, pubmed-meshheading:2171429-Cells, Cultured, pubmed-meshheading:2171429-Dimethyl Sulfoxide, pubmed-meshheading:2171429-Down-Regulation, pubmed-meshheading:2171429-Enzyme Activation, pubmed-meshheading:2171429-Kinetics, pubmed-meshheading:2171429-Kupffer Cells, pubmed-meshheading:2171429-Phorbol 12,13-Dibutyrate, pubmed-meshheading:2171429-Platelet Activating Factor, pubmed-meshheading:2171429-Platelet Membrane Glycoproteins, pubmed-meshheading:2171429-Protein Kinase C, pubmed-meshheading:2171429-Rats, pubmed-meshheading:2171429-Receptors, Cell Surface, pubmed-meshheading:2171429-Receptors, G-Protein-Coupled, pubmed-meshheading:2171429-Tetradecanoylphorbol Acetate

Regulation of platelet-activating factor receptor and PAF receptor-mediated arachidonic acid release by protein kinase C activation in rat Kupffer cells.

Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't