ABSTRACT
Receptor activity-modulating proteins (RAMPs) are accessory molecules that form complexes with specific G protein-coupled receptors (GPCRs) and modulate their functions. It is established that RAMP interacts with the glucagon receptor family of GPCRs but the underlying mechanism is poorly understood. In this study, we used a bioluminescence resonance energy transfer (BRET) approach to comprehensively investigate such interactions. In conjunction with cAMP accumulation, Gα q activation and β-arrestin1/2 recruitment assays, we not only verified the GPCR-RAMP pairs previously reported, but also identified new patterns of GPCR-RAMP interaction. While RAMP1 was able to modify the three signaling events elicited by both glucagon receptor (GCGR) and glucagon-like peptide-1 receptor (GLP-1R), and RAMP2 mainly affected β-arrestin1/2 recruitment by GCGR, GLP-1R and glucagon-like peptide-2 receptor, RAMP3 showed a widespread negative impact on all the family members except for growth hormone-releasing hormone receptor covering the three pathways. Our results suggest that RAMP modulates both G protein dependent and independent signal transduction among the glucagon receptor family members in a receptor-specific manner. Mapping such interactions provides new insights into the role of RAMP in ligand recognition and receptor activation.
ABSTRACT
Objective@#To investigate the delayed effect of liver injury and metabolism of dimethylformamide (DMF) after high exposures in rats.@*Methods@#A total of 12 rats were randomly divided into four groups and 3 rats were in each group. Rats in 1d DMF+2 d delayed group were dosed for 1 day and rested for 2 days, and sacrificed at the 4th day. Rats in 3 d DMF group were dosed for 3 days and sacrificed at the 4th day. Rats in 3 d DMF+3 d delayed group were dosed for 3 days and rested for 3 days, and sacrificed at the 7th day. Rats in control group were administrated with water for 3 days, sacrificed at the 7th day. The administrated dose was 1 000 mg/kg (body weight·d) DMF by oral. The daily observation and body weight were recorded during the study period. After the experiment, the blood biochemistry, including alanine aminotransferase (ALT) , aspartate aminotransferase (AST) , lactic dehydrogenase (LDH) , alkaline phosphatase (ALP) , total bilirubin (TBIL) etc. were detected. Liver weight, kidney weight, liver/body ratio, kidney/body ratio and pathologic examination of liver and kidney were investigated. The concentrations of hemoglobin-adduct (NMHb) were detected.@*Results@#During the period of 1~3 d, body weight growth rate of rats in each treated group had no significant difference with control rats. In the 4~6 th day of the period, rats in group 3 became thinner than before, and the body weight was negative growth (-4.22±3.29 g/d) and significant lower than that of control rats (10.33±3.21 g/d, F=30.07, P<0.05) . AST and LDH levels of 3 d DMF group were significant higher than control group (P<0.05) . Liver/body ratio in 3 d DMF+3 d delayed group were significant higher than control group (P<0.05) . The gross inspection showed 1 rat and 3 rats were observed liver injury in 3 d DMF group and 3 d DMF+3 d delayed group, respectively. Histopathological lesions of 1d DMF+2 d delayed group, 3 d DMF group and 3 d DMF+3 d delayed group were mainly spotty necrosis, focal necrosis and large necrosis of liver cells, respectively. Only NMHb level of control group was undetectable. NMHb levels in 3 d DMF+3 d delayed group were significantly higher than 3 d DMF group (F=135.46, P<0.05) .@*Conclusion@#The DMF-induced liver injury and DMF metabolism may be delayed after high DMF exposures in rats.
ABSTRACT
Objective To establish and evaluate animal model of adult rats with vitamin D deficient and assess the association of vitamin D deficiency and hypertension .Methods Adult SD rats were divided into 3 groups :normal controls group(feed with ordina-ry forage) ,vitamin D deficient groups(feed without vitamin D)and vitamin D control group(feed with vitamin D) ,which were fed with different diets under 12 h:12 h without ultraviolet light bulb(UV-B) .After treatment for 6 weeks ,Retinal blood was collect-ed ,and Serum vitamin D levels was tested by EIA every 2 weeks .Results After treatment for 10 weeks ,Serum level of vitamin D in vitamin D deficient group were reduced to 2 .07 nmol/L ,while vitamin D group and normal control group were measured as 56 .74 nmol/L and 57 .61 nmol/L ,there was no statistically significant difference between vitamin D group and normal control group (P>0 .05) .hypertension of vitamin D deficient group was significantly higher than other two groups .Conclusion It is feasible to estab-lish model of adult rats with vitamin D by UV-B free light and diets control ,hypertension of rats vitamin D deficiency has a signifi-cant rise compared with the control group .
ABSTRACT
There are many problems in the current laboratory diagnostics teaching including unreasonable structure of teaching contents and routinization of teaching methods,etc.This paper explored the laboratory diagnostics teaching reform from the textbooks,teaching subject and teaching focus,in order to better meet the needs of the development of medicine education and clinical practice.