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61.
Calcitonin gene-related peptide and its receptor in the thymus 总被引:2,自引:0,他引:2
Bodo Kurz Brita von Gaudecker Andrea Kranz Brigitte Krisch Rolf Mentlein 《Peptides》1995,16(8):1497-1503
Calcitonin gene-related peptide (CGRP), a 37-amino acid residue neuropeptide, was immunostained in rat thymus at two sites: a subpopulation of thymic epithelial cells, namely subcapsular/perivascular cells, were heavily stained besides some nerve fibers surrounding arteries and arterioles. The administration of nanomolar concentrations of rat -CGRP dose-dependently raised intracellular cyclic adenosine monophosphate (cAMP) levels in isolated rat thymocytes (half-maximum stimulation 1 nM) but not in cultured rat thymic epithelial cells. Peptides structurally related to CGRP (i.e., rat calcitonin or amylin) had no effect. CGRP(8–37), an N-terminally truncated form, acted as an antagonist. Peripheral blood lymphocytes did not respond to CGRP, suggesting that receptors are present only on a subpopulation of thymocytes but not on mature T cells. This was substantiated by visualization of CGRP receptors on single cells by use of CGRP-gold and -biotin conjugates of established biological activity: only a small proportion of isolated thymocytes was surface labeled. In situ, the CGRP conjugates labeled receptors on large thymocytes residing in the outer cortical region of rat thymus pseudolobules. Thus, immunoreactive CGRP is found in subcapsular/perivascular thymic epithelial cells and acts via specific CGRP receptors on thymocytes by raising their intracellular cAMP level. It is suggested that CGRP is a paracrine thymic mediator that might influence the differentiation, maturation, and proliferation of thymocytes. 相似文献
62.
James R. Bunzow Ge Zhang Claudia Bouvier Carmen Saez Oline K. Ronnekleiv Martin J. Kelly David K. Grandy 《Journal of neurochemistry》1995,64(1):14-24
Abstract: We have cloned and expressed a rat brain cDNA, TS11, that encodes a μ-opioid receptor based on pharmacological, physiological, and anatomical criteria. Membranes were prepared from COS-7 cells transiently expressing TS11 bound [3H]diprenorphine with high affinity (KD = 0.23 ± 0.04 nM). The rank order potency of drugs competing with [3H]diprenorphine was as follows: levorphanol (Ki = 0.6 ± 0.2 nM) ≈β-endorphin (Ki = 0.7 ± 0.5 nM) ≈ morphine (Ki = 0.8 ± 0.5 nM) ≈ [d -Ala2, N-Me-Phe4,Gly-ol5]-enkephalin (DAMGO; Ki = 1.6 ± 0.5 nM) ? U50,488 (Ki = 910 ± 0.78 nM) > [d -Pen2,5]-enkephalin (Ki = 3,170 ± 98 nM) > dextrorphan (Ki = 4,100 ± 68 nM). The rank order potencies of these ligands, the stereospecificity of levorphanol, and morphine's subnanomolar Ki are consistent with a μ-opioid binding site. Two additional experiments provided evidence that this opioid-binding site is functionally coupled to G proteins: (a) In COS-7 cells 50 µM 5′-guanylylimidodiphosphate shifted a fraction of receptors with high affinity for DAMGO (IC50 = 3.4 ± 0.5 nM) to a lower-affinity state (IC50 = 89.0 ± 19.0 nM), and (b) exposure of Chinese hamster ovary cells stably expressing the cloned μ-opioid receptor to DAMGO resulted in a dose-dependent, naloxone-sensitive inhibition of forskolin-stimulated cyclic AMP production. The distribution of mRNA corresponding to the μ-opioid receptor encoded by TS11 was determined by in situ hybridization to brain sections prepared from adult female rats. The highest levels of μ-receptor mRNA were detected in the thalamus, medial habenula, and the caudate putamen; however, significant hybridization was also observed in many other brain regions, including the hypothalamus. 相似文献
63.
Conclusion Membrane association is essential for GRK function and because of this the GRKs have evolved complex regulatory mechanisms
for associating with the membrane. Although the GRKs are highly homologous, each kinase utilizes a distinct mechanism for
associating with the membrane, which makes it unique within the family. Initially, the carboxyl terminus of the GRKs was identified
as the “membrane association domain” but recent evidence suggests that the amino terminus may also play a critical role in
localizing the kinases to the membrane (Murga et al., 1996; Pitcher et al, 1996). It is within these two domains that the
GRKs are most variable at the amino acid level. The GRKS exhibit an absolute requirement for phospholipids not only for association
with the membrane but also for activity. There are differences in preference and binding sites for the phospholipids within
the GRK family, which may reflect differential targeting of the GRKs to G protein-coupled receptors situated in different
lipid environments. There are hundreds of G protein-coupled receptors and only six known GRKs. All the GRKs appear to phosphorylate
the same receptor substrates in vitro (Sterne-Marr & Benovic, 1995; Premont et al., 1995). Receptor specificity, in a cellular 相似文献
64.
Characterization of Calpain-Mediated Proteolysis of GluR1 Subunits of α-Amino-3-Hydroxy-5-Methylisoxazole-4-Propionate Receptors in Rat Brain 总被引:1,自引:0,他引:1
Xiaoning Bi Jing Chen Sandeeb Dang Robert J. Wenthold Georges Tocco Michel Baudry 《Journal of neurochemistry》1997,68(4):1484-1494
Abstract: Previous results have indicated that GluR1 subunits of α-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptors are targets of calpain. In the present study, we determined the effects of calpain treatment of synaptic membranes on GluR1 subunits using western blots with antibodies directed against the C-terminal (C-Ab) and the N-terminal (N-Ab) domains of the proteins, and compared them with the effects of calcium treatment of frozen-thawed brain sections. Calpain treatment of synaptic membranes resulted in a large decrease in the GluR1 band (105 kDa) labeled with C-Ab and in the formation of a doublet band labeled with N-Ab due to the appearance of a new species of GluR1 (98 kDa). These effects were blocked almost completely by calpain inhibitors. Calpain-induced changes in GluR1 immunological properties were not associated with modifications of [3 H]AMPA or 6-cyano-7-[3 H]nitroquinoxaline-2,3-dione ([3 H]CNQX) binding. Treatment of frozen-thawed brain sections with concentrations of calcium as low as 0.2 m M resulted in a large decrease in the 105-kDa GluR1 band and in the concurrent appearance of the 98-kDa band. This treatment was associated with increased [3 H]AMPA and [3 H]CNQX binding. These results suggest that there exist several types/states of GluR1 subunits exhibiting different sensitivities to calpain. Our data also indicate the existence of additional calcium-dependent processes regulating the characteristics of receptors in intact tissues. 相似文献
65.
神经生长因子家族及其受体研究进展 总被引:9,自引:0,他引:9
过去几年在神经营养因子、受体和神经元细胞程序性死亡的研究领域中取得了几项引人注目的进展:(1)神经生长因子(NGF)基因家族的其他一些成员包括脑源性神经营养因子(BDNF)、神经营养素-3(NT-3)、神经营养素-4(NT-4)、神经营养素-5(NT-5)的发现;(2)神经生长因子三维结构及功能和进化之关系的阐明;(3)定性了两种神经生长因子受体P75^NGFR和原癌基因p140^trkA以及相关 相似文献
66.
Valerie Brecx Aleksandra Misicka Patricia Verheyden Dirk Tourwé George van Binst 《Letters in Peptide Science》1995,2(3-4):165-168
Summary A new cis-peptide bond mimetic, -benzyl-o-aminomethylphenylacetic acid, was synthesized and incorporated in a homodetic somatostatin analogue. Biological binding tests and 2D NMR conformational analysis indicate that the configuration of the bridge-unit asymmetric center and the orientation of the benzyl side chain play a key role in the biological activity of this type of somatostatin analogues. 相似文献
67.
In vitro autoradiographic localization of [I]-angiotensin II binding sites in the rat and dog kidney
Light microscopic autoradiographic techniques have been utilized to demonstrate specific regions of the rat and dog kidney where angiotensin II receptors exist. Slide mounted tissue sections were labeled with [125I]-angiotensin II using conditions which provided for highly specific binding. These angiotensin II binding sites were localized to several distinct renal structures. In the renal cortex, angiotensin II binding sites were found concentrated in all parts of the glomeruli including the vascular components, the macula densa and the juxtaglomerular apparatus. Angiotensin II binding in the medulla was more diffusely associated with the vasa recta, and to a lesser extent, the thick ascending segment of the loop of Henle. Binding sites specific for angiotensin II were also found in the smooth muscle laminae of the ureter. Scatchard analysis of the binding kinetics allowed the demonstration of two subpopulations of binding sites which differ slightly in their affinities for [125I]-angiotensin II. These subpopulations appear to be associated with distinct components of the renal structure. 相似文献
68.
The biological activities of several ovine chorionic somatomammotropin (oCS) derivatives obtained by chemical modification of the lysine residues were studied by radioreceptor assays using rabbit mammary homogenates (lactogenic activity, L.A.) and liver homogenates (somatotropic activity, S.A.). Even if the control treatment with BH-4 markedly decreased the L.A., it was clear that methylation mainly affected the S.A. and that ethylation reduced both activities. Guanidination inactivated almost completely both activities and acetimidination at a very low degree (3 of 14 lysines) led to less than 50% of both activities. These results show the involvement of lysine residues in the interaction of oCS with lactogenic and somatotropic receptors. 相似文献
69.
A colicin A fragment containing the receptor binding domain can be directed to the periplasmic space in E. coli through gene fusion 总被引:2,自引:0,他引:2
The central region of the colicin A polypeptide chain has been fused to the N-terminal part of beta-lactamase through genetic recombination. This region comprising amino acid residues 70-335 confers on the hybrid protein the ability to protect sensitive cells from the lethal action of colicin A. Although colicin A belongs to the cytoplasmic compartment of E. coli, export of the hybrid protein to the periplasmic space was promoted by the signal peptide of beta-lactamase. 相似文献
70.
Affinity chromatography has been used to isolate and compare the peanut agglutinin receptors from neuraminidase-treated human, bovine and porcine erythrocyte membranes. Passage of Triton X-100-solubilised membrane material through either Sepharose- or acrylamide-based affinity columns resulted in the reversible binding of receptor molecules to the immobilised lectin. Elution with 0.2M galactose released specifically bound glycoprotein fractions, the composition and molecular weights of which were determined by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulphate.Carbohydrate analysis by gas chromatography identified these bound glycoprotein fractions as the major sources of the disaccharide in these membranes. It is suggested that these isolated fractions represent a discrete population of glycoproteins within the membranes studied, which possess both - and carbohydrates. 相似文献