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The kinin receptors are classically involved in inflammation, pain and sepsis. The effects of the kinin B1 receptor agonist des-Arg9-bradykinin (DBK) and lipopolysaccharide (LPS) were investigated by comparing the membrane potential responses of aortic rings from transgenic rats overexpressing the kinin B1 receptor (B1R) in the endothelium (TGR(Tie2B1)) and Sprague Dawley (SD) rats. No difference in the resting membrane potential in the aorta's smooth muscle from the transgenic and SD rats was observed. The aorta rings from SD rats hyperpolarized only to LPS but not to DBK, whereas the aorta rings from TGR(Tie2B1) responded by the administration of both drugs. DBK and LPS responses were inhibited by the B1 receptor antagonist R715 and by iberiotoxin in both cases. Thapsigargin induced a hyperpolarization in the smooth muscle of SD rats that was not reversed by R715, but was reversed by iberiotoxin and this hyperpolarization was further augmented by DBK administration. These results show that the model of overexpression of vascular B1 receptors in the TGR(Tie2B1) rats represent a good model to study the role of functional B1 receptors in the absence of any pathological stimulus. The data also show that KCa channels are the final mediators of the hyperpolarizing responses to DBK and LPS. In addition, we suggest an interaction between the B1R and TLR4, since the hyperpolarization induced by LPS could be abolished in the presence of R715. [ABSTRACT FROM AUTHOR]

The molecular geometrical, vibrational frequency, molecular static polarizability and hyperpolarizability parameters, as well as HOMO-LUMO energies of 4-Aminopyridinium monophthalate (4-APMP) as potential nonlinear optical (NLO) material in the ground state were examined using hybrid GGA, meta-GGA, range-separated hybrid and long-range (LR) corrected models (B3LYP, B3PW91, M062X, HSEh1PBE, CAM-B3LYP, LC-BLYP and ω B97XD levels of density functional theory) with 6-311G(d,p) basis set in order to analyze the effects of different percentage of HF exchange. TD-DFT computations with the PCM (polarizable continuum model) within methanol solvent based on implicit/explicit model and gas phase in the excited state were employed to investigate UV–vis absorption and fluorescence emission wavelengths. Furthermore, by regarding the potential energy distribution (PED), a detailed vibrational study was fulfilled by using VEDA program. Experimental values of structural and spectroscopic parameters of 4-APMP were used to display the effects of the different theoretical methods on the spectroscopic and structural properties. To display the agreement and accuracy of among selected DFT levels and experimental data, the linear correlation coefficients (R 2 ), mean absolute deviation (MAD), overall mean percent deviation (MPD), optimal scaling factor (λ) and overall root mean square (RMS) deviation for structural and vibrational frequency parameters were presented. The NLO parameters indicated that 4-APMP exhibits significant molecular nonlinearity. [ABSTRACT FROM AUTHOR]

To investigate the mechanisms of microwave induced pacemaker cell injuries, Wistar rats and the primary pacemaker cells of newborn Wistar rats were exposed to microwave at average power density of 50 mW/cm 2 . Slower spontaneous beating rate, intercellular Ca 2+ aggregation and cell membrane perforation were detected immediately after the exposure. Moreover, hyperpolarization-activated cyclic nucleotide-gated cation channel 4 (HCN4) was down-regulated immediately after the exposure and up-regulated at 12 h after the exposure. In the sinoatrial node (SAN) of the rats, HCN4 expression increased from day 1 to day 28 after microwave exposure, then declined from 3rd month to 6th month, which was consistent with the changes of ratio of β1-adrenergic receptor (β1-AR) and muscarinic type 2 acetylcholine receptor (M2-AchR). In conclusion, dynamic expression of HCN4, together with changes of β1-AR and M2-AchR expression, was involved in microwave induced pacemaker cell injuries. [ABSTRACT FROM AUTHOR]

To date, no curative psychopharmacologic treatment exists for the core symptoms of autism spectrum disorder (ASD) as well as for schizophrenia. Bumatenide is a specific antagonist of the first isoform of the Na-K-Cl cotransporter (NKCC1). It is usually used as a diuretic but may also promote a decrease in intraneuronal chloride ion concentration leading to hyperpolarization in neuronal membrane and subsequent decrease in neuronal hyperexcitability. This physiologic effect has been considered to be behind the relative efficacy of bumetanide in improving symptoms of ASD and, to a lesser extent, schizophrenia. However, insulin growth factor-1 (IGF-1) shows the same physiologic effect. In addition, it may improve brain network dysconnectivity which is known to be an important neurobiological feature in ASD and schizophrenia. IGF-1 has started to prove its efficacy in improving symptoms of children with Rett syndrome, a genetic disorder that shares several clinical similarities with ASD. IGF-1 may also improve oxytocin secretion through the enhancement of the transient potential receptor V2 channel function. Accordingly, IGF-1 should be studied as a potential treatment of ASD and other mental disorders characterized with brain dysconnectivity such as schizophrenia. [ABSTRACT FROM AUTHOR]