ABSTRACT
The Adrenomedullin peptide hormone has a potent vasodilatory activity. Nevertheless this novel peptide has exposed to be almost a ubiquitous peptide, with the many number of tissues and cell types synthesizing adrenomedullin. Adrenomedullin (ADM) and its related family peptides are calcitonin gene-related peptides (α and β-CGRPs), and intermedin/adrenomedullin-2 (IMD/ADM2) which play vital role as regulators of vascular tone and cardiovascular advances in vertebrates. Current research into their functions in reproduction has acknowledged the function of these peptides and their cognate receptors (calcitonin receptor-like receptor/receptor activity-modifying protein (CLR/RAMP) receptors) in fetal cum maternal blood circulation, feto-placental and uteroimplantation development along with that of female gamete development as well as gamete movement in the oviduct. Moreover, recent findings have enlightened the novelty, potential opportunities for the deterrence and treatment of aberrant pregnancies such as pregnancy-stimulated hypertension, preeclampsia, and IUGR. Conversely, chief efforts are still required to clarify the relationships between evident components of the CLR/RAMP signaling pathway and aberrant pregnancies before CLR/RAMP receptors can develop targets for clinical management. With this comprehension, this review summarizes current progression with specific focus on role of adrenomedullin during early implantation.
ABSTRACT
OBJECTIVE: To observe the effect of liver-soothing and mental-activity-regulating (LSMAR) needling on the expression of receptor activity-modifying protein 1 (RAMP 1, receptor of calcitonin gene-related peptide), 5-hydroxytryptamine 1 D receptor(5-HT 1 DR) in the spinal trigeminal nucleus (STN) and midbrain in migraine rats, so as to explore its underlying mechanism in relieving migraine. METHODS: A total of 40 male Wistar rats were randomly divided into control, model, LSMAR and conventional needling groups (n=10 rats in each). The migraine model was established by subcutaneous injection of nitroglycerin at the posterior neck. LSMAR was applied to "Baihui" (GV 20), bilateral "Fengchi" (GB 20), "Neiguan" (PC 6) and "Taichong" (LR 3) in the LSMAR group and conventional needling was applied to "Baihui" (GV 20) and bilateral "Fengchi" (GB 20) in the conventional acupuncture group for 30 min, once a day for 8 days before modeling. The expression levels of RAMP 1 and 5-HT 1 DR proteins and mRNAs in the STN and mesencephalon were detected by real-time fluorescent quantitative PCR and Western blot, separately. RESULTS: Compared with the control group, the expression levels of RAMP 1 protein and mRNA in STN and mesencephalon were significantly increased (P<0.05) and those of 5-HT 1 DR protein and mRNA considerably decreased (P<0.05) in the model group. After the acupuncture treatment, the increased levels of RAMP 1 protein and mRNA and the decreased levels of 5-HT 1 DR protein and mRNA in the STN and midbrain were obviously reversed in the LSMAR and conventional needling groups relevant to the model group (P<0.05). The effect of LSMAR needling was significantly superior to that of conventional needling in down-regulating the expression levels of RAMP 1 mRNA and protein in the STN and mesencephalon (P<0.05) and in up-regulating the expression levels of 5-HT 1 DR mRNA and protein in the two brain regions (P<0.05). CONCLUSION: Manual acupuncture stimulation of GV 20, GB 20, etc. can inhibit the expression of RAMP 1 protein and mRNA in the STN and midbrain, and up-regulate the expression of 5-HT 1 DR in the two brain regions of migraine rats, which may be related to its effect in relieving migraine.
ABSTRACT
Objective:To investigate the effect of blocking the expression of receptor activity modifying protein 1 (RAMP1 )on calcito-nin gene-related peptide(CGRP)-induced MG-63 cell proliferation.Methods:RAMP1 siRNA was synthesized and screened by tran-scription in vitro.The subcultured MG-63 cells were divided into the following groups:RAMP1 siRNA interference group,empty vector group and blank control group.The mRNA expression and the membrane distribution changes of the calcitonin receptor-like receptor (CRLR)and the receptor component protein (RCP)in MG-63 cells were examined by real-time PCR and immunofluorescence method respectively.Results:RAMP1 and CRLR mRNA and the fluorescence intensity of MG-63 cells decreased after transfection by RAMP1 siRNA(P <0.05).In RAMP1 interference group,the expression of RCP mRNA and the fluorescence intensity were higher than those in the other two groups(P <0.05).After RAMP1 siRNA interference,the proliferation of MG-63 cells was inhibited(P <0.05). Conclusion:RAMP1 siRNA transfection may reduce CRLR expression and inhibite the proliferation of MG-63 cell.
ABSTRACT
Aim Observe the effects of IMD_ 1-53 on acute myocardial injury induced by isoproterenol (ISO). Methods Myocardial ischemia injury in rats was induced by subcutaneous injection with ISO(50 mg?kg -1?d -1, 2days ), and the therapeutic effect of IMD_ 1-53 was observed. Cardiac function was measured. Myocardial cAMP content was determined by radioimmunoassay (RIA). The gene expression of calcitonin receptor-like receptor (CL) and receptor-activity-modifying protein (RAMP1), RAMP2 and RAMP3 in ventricular was determined by semi-quantitative RT-PCR analysis. IMD receptors in cardiac sarcolemmal membrane fractions were assayed [ 125I]-IMD binding studies. Results ISO-treated rats showed lower maximal rate of increase and decrease of left-ventricle pressure development (?LVdp/dt_ max) and higher left-ventricle end-diastolic pressure (LVEDP; all P