ABSTRACT
@#Receptor activity-modifying proteins(RAMPs) are type I transmembrane proteins,which are activity-modifying proteins of a variety of G-protein-coupled receptors(GPCRs).RAMPs are related to physiological and pathological phenomena such as neurological diseases,cardiovascular diseases,renal function,skeletal development and obesity,and of great significance for disease prevention,which are potential targets for the treatment of various diseases and also closely related to the prognosis of diseases.At present,there are few studies on proteins that may regulate the expression of RAMPs.This paper focuses on the sterol regulatory element-binding factor-2(SREBF-2) that may regulate the transcription and expression of RAMP3, and reviews the research progress of RAMPs in biology,pathology and pharmacology,providing a reference for the further research on RAMPs and the prevention and detection of related diseases.
ABSTRACT
Receptor activity modifying proteins (RAMPs) is a kind protein with transmembrane functionality.RAMPs can interact with TypeⅡ G protein coupled receptors (GPCRs) such as calcitonin gene-related peptide receptor (CGRPR),calcitonin receptor (CTR) and calcitonin receptor-like receptor (CRLR),to form a stable heterodimer expression on the cell membrane.Different RAMPs can combine with CRLR or CTR to produce different receptor phenotypes with ligand-specific affinity and thus can decide biological effect of the receptors.In addition,RAMPs can also interact with other GPCRs,which promise broader application in function regulation of G-proteincoupled receptor of RAMPs'.RAMPs' regulation of GPCRs depends on its molecular basis.Our studies of RAMPs provides a new perspective to further researches on GPCRs functionality and CGRP signal transduction.
ABSTRACT
Objective To examine the effects of exogenously administered intermedin (IMD,adrenomedullin-2) on arterial blood pressure,cardiac function and the cardiovascular IMD receptor system in spontaneously hypertensive rats (SHRs) as well as to investigate the associated mechanisms.Methods Thirteen week-old male rats were divided in Wistar Kyoto (WKY) group (n =12),SHR group (n =12),IMD group (SHRs infused with IMD 1-47 500 ng/kg per hour,n =12),and ADM group (SHRs infused with adrenomedullin 500 ng/kg per hour,n =12).Results A two-week continuous administration of low dose IMD 1-47 via mini-osmotic pumps markedly reduced blood pressure,the maximal rates of increase and decrease of left-ventricle pressure development (LV ± dp/dtmax),left ventricular systolic pressure and heart rate in SHRs.Furthermore,IMD also inhibited protein over-expression of cardiovascular IMD receptors,myocardial Receptor Activity-Modifying Proteins (RAMP1 and RAMP2),aortic RAMP1,RAMP2,RAMP3,and calcitonin receptor-like receptor (CRLR);suppressed up-regulation of aortic RAMP1,RAMP2,RAMP3 and CRLR gene expression; and markedly elevated the mRNA abundance of myocardial atrial natriuretic peptide (ANP) and myocardial brain natriuretic peptide (BNP).Additionally,IMD 1-47 administration in SHRs increased aortic cAMP concentration and reduced myocardial cAMP concentration.Conclusion These findings support the speculation that IMD,as a cardiovascular active peptide,is involved in blood pressure reduction and cardiac function amelioration during hypertension.The mechanism underlying this effect may involve IMD binding of a receptor complex formed by RAMPs and CRLR,and consequential regulation of cAMP levels and other cardiovascular active factors,such as ANP and BNP.
ABSTRACT
Objective In the present study we used real-time quantitative RT-PCR to measure the relative expression levels of CGRP,CRLR,RDC-1,RAMP1-3 in periaqueductal gray(PAG)of intact rats. Methods With ?-actin as an endogenous control,write down the C T value and calculate the relative amount of every sample against its endogenous control. Results The results showed the specific amplification of CGRP,CRLR,RAMP1-2 in PAG of rats.Furthermore,the expression of CGRP and RAMP1 is the highest,that of CRLR is higher and the RAMP2 is low;whereas no band is detected in RDC-1 and RAMP3. Conclusion These findings suggest the specific expression of CGRP,CRLR,RAMP1 and RAMP2 mRNA and indicate their functional role in the modulation in PAG of intact rats.