No abstract

Inhibitory effects of root filling materials on the conduction of action potentials evoked in rat phrenic nerves were evaluated in vitro. Endomethasone and N2 Normal completely and irreversibly inhibited conductance; ProcoSol caused complete but reversible inhibition; Kloroperka N-O caused total inhibition which was sometimes reversed; and AH26 and Diaket showed partial inhibition which was partially reversible.

Trefoil factor family 3 (TFF3) is secreted in saliva. The peptide improves the mechanical and chemical resistance of mucins, and it may act as a motility signal for oral keratinocytes during wound healing. This study aimed to identify novel functions of TFF3 in oral keratinocytes. To achieve this, we used phosphoprotein and messenger RNA (mRNA) arrays to compare TFF3-treated and untreated oral keratinocytes. Analysis of the phosphoprotein array indicated that TFF3 signals through the mitogen-activated protein kinases (MAPKs) c-Jun N-terminal kinase (JNK), p38, and extracellular signal-regulated kinase (ERK1/2), and through the phosphoinositide 3-kinase (PI3K)/protein kinase B (PKB) pathway. Microarray analysis of mRNA showed that TFF3 stimulation induced changes in the expression of genes functionally related to cell death/survival, cell growth and proliferation, and cell movement. The reverse transcription-polymerase chain reaction (RT-PCR) results indicated that the transcription of some immediate-early genes (IEGs) was downregulated, whereas the IEGs FBJ osteosarkoma oncogene (FOS) and C-MYC binding protein (MYCBP2) were transiently upregulated by TFF3 stimulation. Together, the results of the arrays indicate that TFF3 is a modifying factor in pathways regulating cell survival, cell growth and proliferation, and cell migration of oral keratinocytes. Trefoil factor family 3 may therefore promote oral wound healing and it should be considered for the treatment of oral ulcerating diseases, or of other diseases.

The water channel aquaporin 5 (AQP5) seems to play a key role in salivary fluid secretion and appears to be critical in the cell volume regulation of acinar cells. Recently, the cation channel transient potential vanilloid receptor 4 (TRPV4) was shown to be functionally connected to AQP5 and also to cell volume regulation in salivary glands. We used the Simian virus 40 (SV40) immortalized cell line SMG C10 from the rat submandibular salivary gland to investigate the effect of ATP and the neurotransmitter analogue carbachol on Ca(2+) signalling and cell volume regulation, as well as the involvement of TRPV4 in the responses. We used fura-2-AM imaging, cell volume measurements, and western blotting. Both carbachol and ATP increased the concentration of intracellular Ca(2+), but no volume changes could be measured. Inhibition of TRPV4 with ruthenium red impaired both ATP- and carbachol-stimulated Ca(2+) signals. Peak Ca(2+) signalling during hyposmotic exposure was significantly decreased following inhibition of TRPV4, while the cells' ability to volume regulate appeared to be unaffected. These results show that in the SMG C10 cells, simulation of nervous stimulation did not induce cell swelling, although the cells had intact volume regulatory mechanisms. Furthermore, even though Ca(2+) signals were not needed for this volume regulation, TRPV4 seems to play a role during ATP and carbachol stimulation.

The membrane 'labilizer' veratridine (3.7 x 10(-5) M) which potentiates the contractions at twitch (0.1 Hz) stimulation due to multiple discharges, inhibited the tetanic contractions (50 Hz in 10 s) and the simultaneously recorded electromyogram in a use-dependent way, leading to fading of tetanic tension. The effect was equal during indirect and direct stimulation, and could therefore be localized to the excitable sarcolemma. This was confirmed by intracellular recording of action potentials, showing a marked veratridine-induced fallout of action potentials during continuous 50 Hz stimulation, whereas endplate potentials were unaffected. Accordingly, veratridine probably caused a use-dependent inhibition of the Na+ channels of the excitable sarcolemma. The tetanic fade was unaffected by K+ depolarization, increased by hyperpolarization in K(+)-free solution, and decreased by high Ca2+. All these changes of the ionic concentrations inhibited the twitch potentiating effect of veratridine. Since hyperpolarization and increasing the electric field in the membrane with high Ca2+ had opposite effects on the tetanic fade, the field change was probably not the cause of the antagonism in high Ca2+. Instead, a membrane stabilizing effect of high Ca2+ is suggested, since the neutral local anaesthetic benzocaine (1.5 x 10(-4) M), which is also a membrane stabilizing drug, had the same effects as high Ca2+ on the veratridine-induced tetanic fade. The effect of veratrine during tetanic stimulation was partly reversible upon washing. The reversibility was enhanced by high Ca2+ or benzocaine.