Concerted enhancement of calcium influx. Neurotransmitter release and protein phosphorylation by a phorbol ester in cultured brain neurons

Interactions between adenosine and phorbol esters or lithium at the frog neuromuscular junction

“…Neither an activator of adenylate cyclase, forskolin (Seamon et al, 1981), nor an inhibitor of adenylate cyclase, MDL 12,330A (Hunt & Evans, 1980) modified the inhibitory effect of adenosine on neuromuscular transmission. The finding that PDAc increases the amplitude and the quantal content of e.p.ps, and thus increases evoked transmitter release, conforms with the results obtained by others using phorbol esters active on protein kinase C either at the neuromuscular junction (Haimann et al, 1987;Shapira et al, 1987;Caratsch et al, 1988) or the central nervous system (Zurgil et al, 1986;Nichols et al, 1987;Huang et al, 1988;Fredholm & Lindgreen, 1988). The enhancement of neuromuscular transmission caused by PDAc, as well as its ability to attenuate the inhibitory effect of adenosine receptor agonists at the neuromuscular junction, might be related to its ability to activate protein kinase C, since (1) the effective concentrations of PDAc at the neuromuscular junction are within the order of magnitude of its affinity for the enzyme (Leach et al, 1983), and (2) the phorbol ester inactive on protein kinase C, PDDec (Castagna et al, 1982), used in a concentration more than 100 times higher than the affinity constant of its active stereoisomer (Leach et al, 1983), did not modify the amplitude of the e.p.ps or the inhibitory action of adenosine on neuromuscular transmission.…”

“…Adenosine might decrease transmitter release either by decreasing calcium entry through calcium channels (Ribeiro et al, 1979;Shinozuka et al, 1985;Gross et al, 1989) or by decreasing the affinity of calcium for an intracellular component of the secretory apparatus (Silinsky, 1984). It is of interest to note that both activation of calcium channels (De Riemer et al, 1985;Zurgil et al, 1986;Huang et al, 1988) and enhanced sensitivity of the stimulus-secretion coupling processes to calcium within the nerve terminal (Nichols et al, 1987), have been proposed as mechanisms to explain the enhancement of neurotransmitter release during activation of protein kinase C by phorbol esters.…”

Phorbol Esters Induce Neurotransmitter Release in Cholinergic Synaptosomes from Torpedo Electric Organ

“…As ACh release induced by TPA could be achieved even in a calcium-free medium, it seems possible that phorbol esters do not affect that process. In fact, it has been reported that TPA failed to increase either a 45Ca2+ uptake in unstimulated brain neurons (Zurgil et al, 1986) or a Ca2+-independent dopamine release from PC12 cells without changes in intracellular free Ca2+ concentrations (Pozzan et al, 1984). Interestingly, TPA-induced phosphorylation of substrates for PKC has been described in cultured brain neurons (Zurgil et al, 1986) and in rat hippocampal slices (Dekker et al, 1989) independent of extracellular Ca2+ or stimulation.…”

Morphine withdrawal in cortical slices: suppression by Ca2+‐channel inhibitors of abstinence‐induced [3H]‐noradrenaline release

“…It has been suggested that these 'recruited' channels are dihydropyridine sensitive. An activation of protein kinase C results in an increased Ca2"-entry and transmitter release in several neuronal preparations (Zurgil et al, 1986;Nichols et al, 1987). During the induction of morphine tolerance, changes of the function of proteinkinase C could occur which could result in changes of membrane permeability to calcium.…”