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Postsynaptic effects of the phorbol ester TPA on frog end-plates

  • Excitable Tissues and Central Nervous Physiology
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Abstract

The effects of the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA), a specific activator of protein kinase C (PKc), were examined on the frog neuromuscular junction. The depolarization elicited by iontophoretically applied acetylcholine (ACh) was reversibly decreased by 20–60% when muscle fibres were exposed to 1–5×10−7 M TPA. Liposome-delivered phosphatidylcholine (100 μg/ml) prevented this effect. A similar decrease in ACh-sensitivity was produced by diacylglycerol (diolein), a physiological activator of PKc, but in this case the decrease was only partially reversible. In TPA-Ringer, (1) the peak size of miniature end-plate potentials exhibited a small decrease; (2) miniature end-plate currents were reduced in size and their decay time constant became longer and relatively independent of membrane potential. The possibility that these TPA-induced actions are mediated by activation of PKc is discussed.

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References

  • Adamo S, Zani BM, Nervi C, Senni MI, Molinaro M, Eusebi F (1985) Acetylcholine stimulates phospholipid inositol turnover at nicotinic receptors of cultured myotubes. FEBS 190:161–164

    Google Scholar 

  • Castagna M, Takai Y, Kaibuchi K, Sano K, Kikkawa U, Nishizuka Y (1982) Direct activation of calcium-activated, phospholipid-dependent protein kinase by tumor-promoting phorbol esters. J Biol Chem 257:7847–7851

    Google Scholar 

  • Colquhoun D, Large WA, Rang HP (1977) An analysis at the action of a false transmitter at the neuromuscular junction. J Physiol (Lond) 266:361–395

    Google Scholar 

  • Cull-Candy SG, Miledi R, Trautmann A (1979) End-plate currents and acetylcholine noise at normal and myasthenic human end-plates. J Physiol (Lond) 287:247–265

    Google Scholar 

  • Davis JS, Clark MR (1983) Activation of protein kinase in the bovine corpus luteum by phospholipid and Ca2+. Biochem J 214:569–574

    Google Scholar 

  • Del Castillo J, Katz B (1955) On the localization of acetylcholine receptors. J Physiol (Lond) 128:159–181

    Google Scholar 

  • Erulkar SD (1983) The modulation of neurotransmitter release at synaptic junctions. Rev Physiol Biochem Pharmacol 98:63–175

    Google Scholar 

  • Eusebi F, Molinaro M, Zani BM (1985) Agents that activate protein kinase C reduce acetylcholine sensitivity in cultured myotubes. J Cell Biol 100:1339–1343

    Google Scholar 

  • Eusebi F, Molinaro M, Caratsch CG (1986) Effects of phorbol ester on spontaneous transmitter release at frog neuromuscular junction. Pflügers Arch 406:181–183

    Google Scholar 

  • Fambrough DM (1979) Control of acetylcholine receptors in skeletal muscle. Physiol Rev 59:165–227

    Google Scholar 

  • Fisher PB, Miranda AF, Mufson RA, Weinstein LS, Fujiki H, Sugimura T, Weinstein IB (1982) Effects of teleocidin and the phorbol ester promoters on cell transformation, differentiation, and phospholipid metabolism. Cancer Res 42:2829–2835

    Google Scholar 

  • Gage PW, Van Helden D (1979) Effects of permeant monovalent cations on end-plate channels. J Physiol 288:509–528

    Google Scholar 

  • Kaibuchi K, Takai Y, Nishizuka Y (1981) Cooperative roles of various membrane phospholipids in the activation of calcium-activated phospholipids-dependent protein kinase. J Biol Chem 256:7146–7149

    Google Scholar 

  • Katz B, Miledi R (1965) Propagation of electric activity in motor nerve terminals. Proc Roy Soc London B 161:453–482

    Google Scholar 

  • Katz B, Miledi R (1972) The statistical nature of the acetylcholine potential and its molecular components. J Physiol (Lond) 224:665–699

    Google Scholar 

  • Katz B, Miledi R (1973) The binding of acetylcholine to receptors and its removal from the synaptic cleft. J Physiol (Lond) 231:549–574

    Google Scholar 

  • Kennedy MB (1983) Experimental approaches to understanding the role of protein phosphorylation in the regulation of neuronal function. Ann Rev Neurosci 6:493–525

    Google Scholar 

  • Kishimoto A, Takai Y, Mori T, Kikkawa U, Nishizuka Y (1980) Activation of calcium and phospholipid-dependent protein kinase by diacylglycerol, its possible relation to phosphatidylinositol turnover. J Biol Chem 255:2273–2276

    Google Scholar 

  • Kordas M (1969) The effect of membrane polarisation on the time course of end-plate current in frog sartorius muscle. J Physiol (Lond) 204:493–502

    Google Scholar 

  • Kupfermann I (1979) Modulatory actions of neurotransmitters. Ann Rev Neurosci 2:447–465

    Google Scholar 

  • Magleby KL, Stevens CF (1972) The effect of voltage on the time course of end-plate currents. J Physiol (Lond) 223:151–171

    Google Scholar 

  • May Jr WS, Sahoun N, Wolf M, Cuatrecasas P (1985) Role of intracellular calcium mobilization in the regulation of protein kinase C-mediated membrane processes. Nature (Lond) 317:549–551

    Google Scholar 

  • Miledi R (1980) Intracellular calcium and desensitization of acetylcholine receptors. Proc Roy Soc London B 209:447–452

    Google Scholar 

  • Miledi R, Parker I (1980) Effects of strontium ions on end-plate channel properties. J Physiol 306:567–577

    Google Scholar 

  • Nestler EJ, Walaas SI, Greengard P (1984) Neuronal phosphoprotein: physiological and clinical implications. Science 225:1357–1364

    Google Scholar 

  • Nishizuka Y (1984a) The role of protein kinase C in cell surface signal transduction and tumor promotion. Nature 308:693–698

    Google Scholar 

  • Nishizuka Y (1984b) Turnover of inositol phospholipids and signal transduction. Science 225:1365–1370

    Google Scholar 

  • Popot J, Changeux J (1984) Nicotinic receptor of acetylcholine: structure of an oligomeric integral membrane protein. Physiol Rev 64:1162–1239

    Google Scholar 

  • Szoka F Jr, Papahadjopoulos D (1978) Procedure for preparation of liposomes with large internal aqueous space and high capture by reverse-phase evaporation. Proc Nat Acad Sci USA 75: 4184–4198

    Google Scholar 

  • Umezawa K, Weinstein IB, Horowitz A, Fujiki H, Matsushima T, Sugimura T (1981) Similarity of teleocidin B and phorbol ester tumour promoters in effects on membrane receptors. Nature 290:411–413

    Google Scholar 

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Caratsch, C.G., Grassi, F., Molinaro, M. et al. Postsynaptic effects of the phorbol ester TPA on frog end-plates. Pflugers Arch. 407, 409–413 (1986). https://doi.org/10.1007/BF00652626

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  • DOI: https://doi.org/10.1007/BF00652626

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