6 mu M, respectively, probably due to an increase of sensitivity of nAChRs for nicotine. We used different concentrations
and durations of exposure to nicotine, due to desensitization of nAChRs directly depends on both these factors. With 500 nM nicotine and 20 min washing periods between nicotine applications, zinc potentiation remained constant, 901% for 2 min and 813% for 20 min of nicotine exposure. With continuous application of nicotine, zinc potentiation decreased as the time of nicotine exposure increased, 721% for 2 min and 254% for 48 min of nicotine exposure. Our results indicate that zinc-potentiating effects on alpha 4 beta 4 nAChRs strongly depend on both concentration and time see more of exposure to nicotine, suggesting that zinc potentiation depends on the degree of desensitization.
(C) 2009 Elsevier Ltd. All rights reserved.”
“Cancer growth dynamics, commonly simulated with a Compertzian model, is analyzed in the framework of a more recent and realistic model. In particular, we consider the setting of a tumor embedded in a host organ and investigate their interaction. We assume that, at least in some cases, tumor metastasis AZD0156 may be triggered by an ‘energetic crisis’, when the tumor exceeds the ‘carrying capacity’ of the host organ. As a consequence, dissemination of clusters of cancer cells is set in motion, with a statistical probability given by a Poisson distribution. The model, although still at a preclinical level, is fully quantitative and is applied, as an example, to the case of prostate cancer. The results confirm that, at least for the more aggressive cancers, metastasis starts very early during tumorigenesis and a quantitative link is found between the tumor’s doubling time, its ‘aggressiveness’ and the metastatic potential., (c) 2008 Elsevier Ltd. All rights reserved.”
“The
alpha 4 subunit of the GABA(A) Sclareol receptor (GABAR) is capable of rapid plasticity, increased by chronic exposure to positive GABA modulators, such as the neurosteroid 3 alpha-OH-5 alpha[beta]-pregnan-20-one (THP). Here, we show that 48 h exposure of differentiated neuroblastoma cells (IMR-32) to 100 nM THP increases alpha 4 expression, without changing the current density or the concentration-response curve. Increased expression of alpha 4-containing GABAR was verified by a relative insensitivity of GABA (EC20)-gated current to modulation by the benzodiazepine (BZ) lorazepam (0.01-100 mu M), and potentiation of current by flumazenil and RO15-4513, characteristic of alpha 4 beta gamma 2 pharmacology. In contrast to THP, compounds which decrease GABA-gated current, such as the BZ inverse agonist DMCM, the GABAR antagonist gabazine and the open channel blocker penicillin, decreased alpha 4 expression after a 48 h exposure, without changing BZ responsiveness. However, pentobarbital, another positive GABA modulator, increased alpha 4 expression, while the BZ antagonist flumazenil had no effect.