The results in this study show that the rhodamine fluorophore can be specifically conjugated to Angiotensin II at Lys3 residue (substituted for a Val) without altering the biological activity of the parent compound. The conjugated peptide was characterized using HPLC, mass spectrometry, and N-terminal sequencing. The rhodamine-Angiotensin II binds effectively to AT1 receptor and gets internalized in clathrin coated vesicles by endocytosis. These results clearly suggest the usefulness of fluorophore-conjugated peptides in studies such as, ligand-receptor binding, and ligand-receptor complex internalization, for drug delivery using cell receptors and as an alternative to peptide hormone radioimmunoassays. 相似文献
The present study was conducted to evaluate sublethal effects of B-azolemiteacrylic on the two-spotted spider mite, Tetranychus urticae Koch (Acari: Tetranychidae). Female adults of T. urticae were exposed to LC10 and LC30 of the acaricide, and the effects on treated females and their offspring were evaluated. The results showed that the fecundity of F0 female adults treated with LC10 and LC30 of B-azolemiteacrylic was reduced by 30.9 and 39.2%, respectively. Longevity and oviposition period of the females were significantly reduced as well. The developmental duration of egg and deutonymph stage of the F1 generation were not significantly different from that of the control. The protonymph stage after LC30 treatment lasted significantly longer, whereas the larva, deutonymph and female stage were significantly shorter than the control. The oviposition period of the F1 generation was significantly shortened, the fecundity of each female decreased significantly, and the ratio of female-to-male was reduced too. Moreover, the average generation period of T. urticae after LC10 and LC30 treatments was shorter than that of the control, and the net production rate (R0), intrinsic rate of increase (rm) and finite rate of increase (λ) were all reduced by 33.3, 7.5 and 1.9% (LC10 treatment) and by 51.3, 14.8 and 3.6% (LC30 treatment), respectively. The population doubling time was prolonged by 7.5 and 14.8% after LC10 and LC30 treatments, respectively, compared with the control. These results indicate that B-azolemiteacrylic may effectively inhibit the development rate of the F0 and F1 populations of T. urticae, which will help design integrated strategies for the comprehensive control of T. urticae and rational use of pesticides in the field.
Acid-sensing ion channels (ASICs), activated by lowering extracellular pH (pH(o)), play an important role in normal synaptic transmission in brain and in the pathology of brain ischemia. Like pH(o), intracellular pH (pH(i)) changes dramatically in both physiological and pathological conditions. Although it is known that a drop in pH(o) activates the ASICs, it is not clear whether alterations of pH(i) have an effect on these channels. Here we demonstrate that the overall activities of ASICs, including channel activation, inactivation, and recovery from desensitization, are tightly regulated by pH(i). In cultured mouse cortical neurons, bath perfusion of the intracellular alkalizing agent quinine increased the amplitude of the ASIC current by approximately 50%. In contrast, intracellular acidification by withdrawal of NH(4)Cl or perfusion of propionate inhibited the current. Increasing pH buffering capacity in the pipette solution with 40 mm HEPES attenuated the effects of quinine and NH(4)Cl. The effects of intracellular alkalizing/acidifying agents were mimicked by using intracellular solutions with pH directly buffered at high/low values. Increasing pH(i) induced a shift in H(+) dose-response curve toward less acidic pH but a shift in the steady state inactivation curve toward more acidic pH. In addition, alkalizing pH(i) induced an increase in the recovery rate of ASICs from desensitization. Consistent with its effect on the ASIC current, changing pH(i) has a significant influence on the acid-induced increase of intracellular Ca(2+), membrane depolarization, and acidosis-mediated neuronal injury. Our findings suggest that changes in pH(i) may play an important role in determining the overall function of ASICs in both physiological and pathological conditions. 相似文献
The sulfonylurea receptor (SUR1) of the pancreatic beta-cell ATP-sensitive potassium channel plays a key role in glucose-induced insulin secretion. The A-allele of a single nucleotide polymorphism (SNP) in exon 31 of the SUR1 gene (AGG-->AGA; Arg1273Arg) has previously been shown to be associated with hyperinsulinemia in nondiabetic Mexican-American subjects. Here, we have investigated the association of this SNP with type 2 diabetes mellitus (T2DM) in French Caucasian subjects. We have observed an increased frequency of the A allele (37.1% vs 27.6%, P=0.0048; odds ratio 1.54), of the AA genotype (15.7% vs 9.8%; P=0.025), and of the combined AA/AG genotypes (58.5% vs 45.5%, P=0.0098; odds ratio 1.69) in patients compared with controls. This association is stronger in the subgroup of patients with age of diagnosis of diabetes equal to or less than 45 years: A allele 43.2% (P=0.0003 compared with controls; odds ratio 1.99), AA genotype 21.4% (P=0.0032), and combined AA/AG genotypes 65.1% (P=0.0022; odds ratio 2.23). Unexpectedly, the G allele is strongly associated with arterial hypertension in obese diabetic subjects (GG vs AA odds ratio 19.97). In conclusion, we have observed an association of an SNP in exon 31 of the SUR1 gene with T2DM. These data reinforce the hypothesis that insulin secretion defects in T2DM might be at least partially related to allelic variations in the SUR1 gene. 相似文献
This study was to explore whether repeated non-invasive limb ischemic pre-conditioning (NLIP) can confer an equivalent cardioprotection against myocardial ischemia-reperfusion (I/R) injury in acute diabetic rats to the extent of conventional myocardial ischemic pre-conditioning (MIP) and whether or not the delayed protection of NLIP is mediated by reducing myocardial oxidative stress after ischemia-reperfusion. Streptozotocin-induced diabetic rats were randomized to four groups: Sham group, the I/R group, the MIP group and the NLIP group. Compared with the I/R group, both the NLIP and MIP groups showed an amelioration of ventricular arrhythmia, reduced myocardial infarct size, increased activities of total superoxide dismutase (SOD), manganese-SOD and glutathione peroxidase, increased expression of manganese-SOD mRNA and decreased xanthine oxidase activity and malondialdehyde concentration (All p < 0.05 vs I/R group). It is concluded that non-invasive limb ischemic pre-conditioning reduces oxidative stress and attenuates myocardium ischemia-reperfusion injury in diabetic rats. 相似文献