The recent discovery of mammalian bitter, sweet, and umami taste receptors indicates how the different taste qualities are encoded at the periphery. However, taste representations in the brain remain elusive. We used a genetic approach to visualize the neuronal circuitries of bitter and sweet tastes in mice to gain insight into how taste recognition is accomplished in the brain. By selectively expressing a transsynaptic tracer in either bitter- or sweet and/or umami-responsive taste receptor cells, and by comparing the locations of the tracer-labeled neurons in the brain, our data revealed the potential neuronal bases that underlie discrimination of bitter versus sweet.
The effect of tumor promoters on electrical coupling between human FL cells was investigated with a microelectrode technique. When a low concentration (100 ng/ml) of 12-O-tetradecanoylphorbol 13-acetate (TPA) was added to culture medium, only 6% of the cells showed electrical coupling after 5 hr, whereas in control medium more than 90% of the cells were coupled. In the presence of TPA, cell coupling remained suppressed for at least another 19 hr. When TPA was washed out from the culture medium, the cells commenced electrical coupling: 90% of the cells were coupled within 4 hr of the removal of TPA, a rate very similar to that of nontreated control cells. Therefore, TPA-mediated inhibition of cell coupling is reversible. When TPA was added to a culture in which more than 90% of the cells had already established electrical coupling, the percentage of coupled cells decreased to 6% within 8 hr, indicating that TPA can also diminish already established cell coupling. Inhibition of cell coupling also was achieved with other mouse skin tumor promoters--phorbol 12,13-didecanoate, ingenol dibenzoate, and mezerein--whereas nonpromoting derivatives--phorbol and 4 alpha-phorbol 12,13-didecanoate-showed no effect. None of these compounds changed the membrane potential, membrane resistance, or growth rate of FL cells. Thus, it appears that TPA and structurally-related tumor promoters specifically disturb the formation or function, or both, of cell-cell junctions, without significantly affecting the general properties of the surface membrane or the growth of FL cells.
Our previous report has shown that Irsogladine maleate (IM) counters and obviates the reduction in gap junction intercellular communication (GJIC) and the increase in IL-8 levels, respectively, induced by outer membrane protein 29 from Actinobacillus actinomycetemcomitans (A. actinomycetemcomitans) in cultured human gingival epithelial cells (HGEC). In addition, IM suppresses the increase in the secretion of IL-8 caused by whole live A. actinomycetemcomitans. These findings implicate the modulation of IL-8 levels by IM in abolishment of the reduction of GJIC in HGEC. Tight junctions are also responsible for cell-cell communication. Zonula occludens protein-1 (ZO-1) is a major tight junction protein. To investigate the regulatory mechanism of intercellular communication mediated by IM, in the present study, we focused on the involvement of IL-8 in A. actinomycetemcomitans-induced change in GJIC and ZO-1 expression in HGEC. IM countered the A. actinomycetemcomitans-induced reduction in levels of Connexin (CX) 43, suggesting that it could abolish the A. actinomycetemcomitans-induced reduction in GJIC in HGEC. CXCR-1 is a receptor of IL-8. The simultaneous addition of A. actinomycetemcomitans and anti-CXCR-1 antibody also abrogated the repression of GJIC and CX43 expression by A. actinomycetemcomitans in HGEC, although the anti-CXCR-1 antibody was less effective than IM. IM inhibited the IL-8-induced reduction in CX43 levels and GJIC in HGEC. IM countered the A. actinomycetemcomitans-induced reduction in the expression of ZO-1, although anti-CXCR-1 antibody did not influence the decrease in ZO-1 mRNA levels caused by A. actinomycetemcomitans. Furthermore, IL-8 had little effect on the mRNA levels of ZO-1. These findings suggest that IL-8 mediates the A. actinomycetemcomitans-induced reduction of GJIC and CX43 expression in HGEC. The regulation of IL-8 levels by IM in HGEC is partially involved in abrogation of the reduction of GJIC and CX43 expression by A. actinomycetemcomitans. Furthermore, the regulatory effect of IM on the expression of CX43 and ZO-1 is different.
Isoproterenol (IPR) and 8-(4-chlorophenylthio)-cyclic AMP (cpt-cAMP) enhanced carbachol (CCh)-induced fluid secretion from rat parotid glands, but had no effect by themselves. The enhancement by IPR was blocked by propranolol. In dispersed parotid acinar cells, IPR and cpt-cAMP potentiated CCh-induced K+ and Cl- currents (IK and ICl). IPR at the concentration of 0.1 microM significantly potentiated the CCh-induced increase in intracellular Ca2+ concentration ([Ca2+]i), but 1 mm cpt-cAMP did not. The incidence of the potentiation by IPR in CCh-induced Mn2+ entry was 31% and that by cpt-cAMP was 21%. The potentiation by IPR in the ionic currents and the [Ca2+]i was suppressed by propranolol. These results suggest that the CCh-induced fluid secretion from rat parotid glands is enhanced by IPR through the potentiation of IK and ICl mainly by the increased cyclic AMP level and partially by the potentiated Ca2+ influx and [Ca2+]i increase, and that IPR is more effective than cpt-cAMP in the enhancement of the CCh-induced [Ca2+]i increase.
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