Phorbol esters and K+ up-regulate alpha-bungarotoxin binding sites in cultured chromaffin cells through a related mechanism.
Nicotinic alpha-bungarotoxin (alpha-BGT) receptors in cultured chromaffin cells are up-regulated in response to long term (days) exposure to nicotinic antagonists, elevated K+, and activators of protein kinase C (PKC), such as the phorbol ester, 4 beta-phorbol 12-myristate 13-acetate (PMA). The present experiments were done to determine whether their was any interaction in the ability of PMA and K+ to up-regulate the alpha-BGT receptors. Chromaffin cells were treated for 3 days with both 100 nM PMA and 20 mM K+, concentrations which produce maximal responses on their own. The increase in alpha-BGT binding after the combined treatment was the same as that seen with K+ alone suggesting that K+ inhibited the PMA-mediated effect. The K(+)-induced increase in toxin binding was partially prevented by polymyxin B, an agent which completely inhibited the PMA induced increase. The time courses of the increases in binding induced by both K+ and PMA were similar in that the most marked increases in binding were observed at the later time points. The PMA-induced up-regulation was partially inhibited by an activator of adenylate cyclase, a result similar to that previously seen with K+. The present studies suggest that the up-regulation of alpha-BGT receptors induced by K+ shares similarities with that induced by phorbol esters. The observations that K+ inhibited the PMA induced increase and that a PKC inhibitor partially blocked the K+ response suggest that the K+ and PMA mediated induction of the alpha-BGT sites may be linked with the effects of K+ preceding those of PMA.
Geertsen
S
S
Department of Pharmacology, McGill University, Montreal, Que., Canada.
Trifaro
J M
JM
Quik
M
M
D000313:Adrenal Medulla / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D002038:Bungarotoxins / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004789:Enzyme Activation; D007700:Kinetics; D011112:Polymyxin B / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects*; D064569:alpha7 Nicotinic Acetylcholine Receptor
D002038:Bungarotoxins; D004268:DNA-Binding Proteins; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; D005576:Colforsin; D011493:Protein Kinase C; D011112:Polymyxin B; D013755:Tetradecanoylphorbol Acetate; D011188:Potassium