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排序方式: 共有222条查询结果,搜索用时 15 毫秒
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Identification and pharmacological characterization of prokineticin 2 beta as a selective ligand for prokineticin receptor 1 总被引:4,自引:0,他引:4
Chen J Kuei C Sutton S Wilson S Yu J Kamme F Mazur C Lovenberg T Liu C 《Molecular pharmacology》2005,67(6):2070-2076
Prokineticins 1 and 2 (PK1 and PK2) have been recently identified from humans and other mammals and play multiple functional roles. PK proteins are ligands for two G protein-coupled receptors, PK receptor 1 (PKR1) and PK receptor 2 (PKR2). Here, we report the molecular cloning and pharmacological characterization of an alternatively spliced product of the PK2 gene encoding 21 additional amino acids compared with PK2, designated PK2L (for PK2 long form). PK2L mRNA is broadly expressed, as is PK2. However, PK2L mRNA expression is lower in brain, undetectable in kidney, and much higher in lung and spleen than that of PK2. We expressed PK2L in mammalian cells and characterized the resulting peptide in comparison with PK1 and PK2. Biochemical characterization indicates that secreted PK2L protein is processed into a smaller peptide by proteolytic cleavage. We designate this smaller form of peptide as PK2beta. Coexpression of furin with PK2L significantly increased the PK2beta processing efficiency. Functional studies showed that PK1, PK2, and PK2beta stimulate intracellular Ca(2+) responses in PKR1-expressing cells with similar potencies. However, the PK2beta stimulus of Ca(2+) responses in PKR2-expressing cells is at least 10-fold less potent than that of PK1 or PK2. Differences in receptor selectivity combined with differential tissue expression patterns suggest PK2 and PK2beta might have different functions in vivo. PKRs have been reported to couple to G(q) and G(i) proteins. In this report, we show that PKs not only stimulate Ca(2+) mobilization but also induce cAMP accumulation in PKR-expressing cells. 相似文献
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Chen J Kuei C Sutton SW Bonaventure P Nepomuceno D Eriste E Sillard R Lovenberg TW Liu C 《The Journal of pharmacology and experimental therapeutics》2005,312(1):83-95
Relaxin-3 has recently been identified as a ligand for two structurally related G-protein-coupled receptors, human GPCR135 and GPCR142. This current study reports the characterization of mouse and rat GPCR135 as well as GPCR142 from mouse, monkey, cow, and pig at the molecular and pharmacological levels. Mouse and rat GPCR135 exhibit high homology (>85%) to the human GPCR135 and have very similar pharmacological properties to that of the human GPCR135. Human and mouse/rat relaxin-3 both bind to and activate mouse, rat, and human GPCR135 at high affinity with IC(50) or EC(50) values close to 0.5 nM. In contrast, the mouse GPCR142 is less well conserved (74% homology) with human GPCR142. The rat GPCR142 gene was found to be a pseudogene. We further cloned GPCR142 genes from monkey, cow, and pig and found that they are highly homologous (>84%) to human GPCR142. Pharmacological characterization of GPCR142 from different species demonstrated that relaxin-3 binds to GPCR142 from different species at high affinity (IC(50) < 5 nM). However, relaxin-3 does not stimulate a Ca(2+) response in cells coexpressing Galpha(16) and mouse GPCR142, whereas it does for cells expressing GPCR142 from other species tested. Our results suggest that GPCR142 may have a diminished role as a receptor for relaxin-3 in rodents, or perhaps GPCR142 functions as a receptor for another ligand in nonrodents. Boels and Schaller recently reported bradykinin as a ligand for GPCR142 (also known as GPR100). In this report, we demonstrate that bradykinin activates neither GPCR135 nor GPCR142, whereas relaxin-3 does. 相似文献
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Liu KS Kao CH Liu SY Sung KC Kuei CH Wang JJ 《The Journal of pharmacy and pharmacology》2006,58(3):337-344
Buprenorphine is a promising new pharmacotherapy for the management of physical dependence to opioids. The aim of the study was to evaluate the duration of action of several novel depots of buprenorphine in the treatment of physical dependence to morphine in mice. Following intramuscular injection, the duration of action of several novel oil-based depots of buprenorphine base in morphine-dependent mice were evaluated. The traditional dosage form of buprenorphine hydrochloride in saline was used as control. We found that the depot of buprenorphine base in sesame oil produced a dose-related long-lasting effect. On an equimolar basis of 6 micromol kg(-1), its effect was 5.7-fold longer than that of buprenorphine hydrochloride in saline. When prepared in several other oleaginous vehicles (castor oil, cottonseed oil, peanut oil and soybean oil), buprenorphine base also produced a long-lasting effect, which was similar to buprenorphine base in sesame oil. In conclusion, buprenorphine base, when prepared in oleaginous vehicles and injected intramuscularly in mice, produced a long-lasting effect on physical dependence to morphine. 相似文献
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A pediatric trial of radiation/cetuximab followed by irinotecan/cetuximab in newly diagnosed diffuse pontine gliomas and high‐grade astrocytomas: A Pediatric Oncology Experimental Therapeutics Investigators' Consortium study 下载免费PDF全文
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The effect of a researcher designated music intervention on hospitalised psychiatric patients with different levels of anxiety 下载免费PDF全文