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At least 1,495 records · Page 83Linked to original sources
PubMed1995

Continuous subcutaneous administration of the N-methyl-D-aspartic acid (NMDA) receptor antagonist ketamine in the treatment of post-herpetic neuralgia.

The effect of continuous subcutaneous (s.c.) infusion of ketamine on nerve injury pain was examined in patients with post-herpetic neuralgia. Five patients that reported pain relief after acute intravenous injection of ketamine were included in this open prospective study. Ketamine was administered continuously in increasing doses using a portable infusion pump (CADD-PLUS, Pharmacia), and the treatment period for each infusion rate (0.05, 0.075, 0.10, or 0.15 mg/kg/h) was 7 days and nights. Relief of continuous pain, as evaluated daily by visual analogue scales, was observed at the infusion rate of 0.05 mg/kg/h, but was most marked during infusion of 0.15 mg/kg/h. All the patients reported that ketamine reduced the severity of continuous pain as well as reduced the severity and number of attacks of spontaneous pain. Changes in evoked pain (allodynia and wind-up-like pain) were recorded before change of infusion rate. Allodynia was maximally reduced 59-100% after 1 week infusion of 0.05 mg/kg/h, and wind-up-like pain was maximally reduced 60-100% after 1 week infusion of 0.15 mg/kg/h. Itching and painful indurations at the injection site was the most bothersome side-effect and for this reason 1 patient discontinued treatment after 2 weeks. Other common side-effects were nausea, fatigue and dizziness. The present results show that continuous, spontaneous and evoked pain in patients with post-herpetic neuralgia is reduced by continuous s.c. infusion of ketamine, but is associated with intolerable side effects.

Aged↗
PubMed1995

Site-directed mutagenesis of the arginine-glycine-aspartic acid sequence in osteopontin destroys cell adhesion and migration functions.

Osteopontin (OPN) is a secreted calcium-binding phosphoprotein produced in a variety of normal and pathological contexts, including tissue mineralization and cancer. OPN contains a conserved RGD (arg-gly-asp) amino acid sequence that has been implicated in binding of OPN to cell surface integrins. To determine whether the RGD sequence in OPN is required for adhesive and chemotactic functions, we have introduced two site-directed mutations in the RGD site of the mouse OPN cDNA, in which the RGD sequence was either deleted or mutated to RGE (arg-gly-glu). In order to test the effect of these mutations on OPN function, we expressed control and mutated mouse OPN in E. coli as recombinant glutathione-S-transferase (GST)-OPN fusion proteins. Control mouse GST-OPN was functional in cell adhesion assays, supporting attachment and spreading of mouse (malignant PAP2 ras-transformed NIH 3T3, and, to a lesser extent, normal NIH 3T3 fibroblasts) and human (MDA-MB-435 breast cancer, and normal gingival fibroblast) cells. In contrast, neither of the RGD-mutated OPN proteins ("delRGD" or "RGE") supported adhesion of any of the cell lines, even when used at high concentrations or for long assay times. GRGDS (gly-arg-gly-asp-ser) peptides inhibited cell adhesion to intact GST-OPN, as well as to fibronectin and vitronectin. In chemotaxis assays, GST-OPN promoted directed cell migration of both malignant (PAP2, MDA-MB-435) and normal (gingival fibroblast, and NIH 3T3) cells, while RGD-mutated OPN proteins did not. Together these results suggest that the conserved RGD sequence in OPN is required for the majority of the protein's cell attachment and migration-stimulating functions.

3T3 Cells↗
PubMed1990

Expression of c-fos protein by N-methyl-D-aspartic acid in hypothalamus of immature female rats: blockade by MK-801 or neonatal treatment with monosodium glutamate.

Significant NMDA-induced cellular activity in the median eminence-arcuate region of immature female rats was immunocytochemically localized via c-fos protein-like immunoreactivity. The production of this protein was completely prevented by pre-injection of MK-801 or APV, antagonists of the NMDA receptor-coupled ion channel. Treatment of newborn rats with monosodium glutamate (MSG), which destroys glutamate-sensitive neurons, significantly attenuated NMDA-induced c-fos when tested in the peripubertal period. These results implicate NMDA receptors in the expression of c-fos protein-like immunoreactivity in cells of the arcuate nucleus-median eminence of immature female rats.

Aging↗
PubMed1991

Arginyl-glycyl-aspartic acid (RGD): a cell adhesion motif.

The tripeptide Arg-Gly-Asp (RGD) was originally identified as the sequence within fibronectin that mediates cell attachment. The RGD motif has now been found in numerous other proteins and supports cell adhesion in many, but not all, of these. The integrins, a family of cell-surface proteins, act as receptors for cell adhesion molecules. A subset of the integrins recognize the RGD motif within their ligands, the binding of which mediates both cell-substratum and cell-cell interactions. RGD peptides and mimetics, in addition to providing insights into the fundamental mechanisms of cell adhesion, are potential therapeutic agents for the treatment of diseases such as thrombosis and cancer.

Amino Acid Sequence↗
PubMed1996

A recombinant, arginine-glycine-aspartic acid (RGD) motif from foot-and-mouth disease virus binds mammalian cells through vitronectin and, to a lower extent, fibronectin receptors.

The cell-binding abilities of a recombinant, RGD-containing peptide from foot-and-mouth disease virus (FMDV) have been characterized in HeLa and BHK cells. This peptide represents the aa sequence of the solvent-exposed G-H loop of protein VP1 which is involved in cell recognition and infection. The efficiency of the viral motif in promoting cell attachment and spreading is comparable to that shown by fibronectin or vitronectin. Cell binding is inhibited by a monoclonal antibody directed against a viral, RGD-involving B-cell epitope and also by sera against vitronectin (alpha V beta 3/beta 5) and fibronectin (alpha 5 beta 1) receptors. In addition, a synthetic RGD peptide, which is a ligand for both integrins, prevents the cell binding mediated by the FMDV domain. These data demonstrate that the FMDV RGD motif is a potent ligand for cell-receptor integrins and sufficient to promote cell attachment to susceptible cells mainly through the vitronectin receptor.

Amino Acid Sequence↗
PubMed1991

Cyclic parathyroid hormone related protein antagonists: lysine 13 to aspartic acid 17 [i to (i + 4)] side chain to side chain lactamization.

Cyclization of parathyroid hormone related protein (7-34)amide [PTHrP(7-34)NH2] via covalent bond formation between the epsilon-amino of Lys13 and the beta-carboxyl of Asp17 yielded a 20-membered ring lactam. This analogue, [Lys13,Asp17]PTHrP(7-34)NH2, was 5-10-fold more potent than the linear parent peptide (Kb = 15 and 18 nM in PTH receptor binding assays, and Ki = 130 and 17 nM in PTH-stimulated adenylate cyclase assays in bovine renal cortical membrane and in human bone derived B10 cells, respectively). In contrast, a linear analogue in which charges in positions 13 and 17 were eliminated and other stereoisomers of the above-mentioned lactam in which either Lys13 and/or Asp17 were replaced by the corresponding D-amino acids were much less potent with regard to antagonist bioactivity than the parent peptide. The rationale for the design of the lactam as well as the conformational implications for the PTHrP sequence in light of reported models suggested for the 1-34 peptide are described. The potential use of conformationally constrained analogues for elucidating the "bioactive conformation" of antagonists and for the design of substantially simplified molecular structures for antagonists is discussed.

Adenylyl Cyclases↗
PubMed1988

Structure-function relationships in the Na,K-ATPase alpha subunit: site-directed mutagenesis of glutamine-111 to arginine and asparagine-122 to aspartic acid generates a ouabain-resistant enzyme.

Na,K-ATPases from various species differ greatly in their sensitivity to cardiac glycosides such as ouabain. The sheep and human enzymes are a thousand times more sensitive than the corresponding ones from rat and mouse. To define the region of the alpha 1 subunit responsible for this differential sensitivity, chimeric cDNAs of sheep and rat were constructed and expressed in ouabain-sensitive HeLa cells. The construct containing the amino-terminal half of the rat alpha 1 subunit coding region and carboxyl-terminal half of the sheep conferred the ouabain-resistant phenotype to HeLa cells while the reverse construct did not. This indicates that the determinants involved in ouabain sensitivity are located in the amino-terminal half of the Na,K-ATPase alpha subunit. By use of site-directed mutagenesis, the amino acid sequence of the first extracellular domain (H1-H2) of the sheep alpha 1 subunit, Gln-Ala-Ala-Thr-Glu-Glu-Glu-Pro-Gln-Asn-Asp-Asn, was changed to that of the rat, Arg-Ser-Ala-Thr-Glu-Glu-Glu-Pro-Pro-Asn-Asp-Asp. When expressed in HeLa cells, this mutated sheep alpha 1 construct, like the rat/sheep chimera, was able to confer ouabain resistance to these cells. Furthermore, similar results were observed when HeLa cells were transfected with a sheep alpha 1 cDNA containing only two amino acid substitutions. This double mutation was a Gln-111----Arg and Asn-122----Asp change at the amino terminus and carboxyl terminus, respectively, of the H1-H2 extracellular region. The resistant cells, whether transfected with the rat alpha 1 cDNA, the rat/sheep chimera, or the mutant sheep alpha 1 cDNAs, exhibited identical biochemical characteristics including ouabain-inhibitable cell growth, 86Rb+ uptake, and Na,K-ATPase activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1981

Photochemical inactivation of the angiotensin receptor of rabbit aorta by N alpha-(2-nitro-5-azidobenzoyl)-[1-aspartic acid,5-isoleucine]angiotensin II.

The photoaffinity label N alpha-(2-nitro-5-azidobenzoyl)-[Asp1,Ile5]angiotensin II (nitroazidobenzoyl-angiotensin II) has a pD2 of 7.22 in the rabbit aortic strip assay compared to 8.44 for [Asp1,Ile5]angiotensin II and can be completely inhibited by [Sar1, Ala8]angiotensin II. Photolysis of a single dose of nitroazidobenzoyl-angiotensin II (0.1 microM) with aortic strips for 3 min with light of wavelengths of greater than 320 nm, followed by washing, resulted in loss of approximately 25% of the strip's response to a subsequent dose of nitroazidobenzoyl-angiotensin II. Photolysis of three consecutive doses of label resulted in loss of 62% of the strips response to a subsequent dose. Repetitive exposure to label in the dark and repetitive photolyses without label resulted in loss of no more than 20% of the strips ability to respond to angiotensin II. Photolysis with three consecutive doses of 0.1 microM nitroazidobenzoyl-angiotensin II in the presence of 0.5 microM of the competitive inhibitor [Sar1,Ala8]angiotensin II decreased the observed inhibition from 62 to 22%. The long-lasting inhibition observed after photolysis with 0.1 microM nitroazidobenzoyl-angiotensin II therefore occurred via photolysis of some part of the nitroazidobenzoyl chromophore. This inhibition was mediated via the receptor that binds [Sar1,Ala8]angiotensin II and, therefore, angiotensin II.

Affinity Labels↗
PubMed1977

Synthesis and specific pressor activity of [1-aspartic acid,5-valine,9-serine]angiotensin I ("fowl angiotensin I").

[Asp1, Val5, Ser9]angiotensin I was synthesized by Merrifield's solid-phase procedure. The dansylated derivative of this angiotensin was cochromatographed on the TLC with the dansylated angiotensin decapeptide isolated from white leghorn fowl. Either angiotensin showed identical behavior. The per mole pressor activity of the synthetic decapeptide (in rats anesthetized with pentobarbital and treated with pentolinium) as compared to mammalian angiotensins, namely, [Ile5]angiotensin I, [Val5]angiotensin I, [Ile5]angiotensin II, and [Val5]angiotensin II, was 157, 181, 114, and 85%, respectively.

Angiotensin II↗
PubMed1992

Gelsolin-derived familial amyloidosis caused by asparagine or tyrosine substitution for aspartic acid at residue 187.

Dominantly inherited familial amyloidosis, Finnish type (FAF) is caused by the accumulation of a 71-amino acid amyloidogenic fragment of mutant gelsolin (GSN). FAF is common in Finland but is very rare elsewhere. In Finland and in two American families, the mutation is a G654A transition leading to an Asp to Asn substitution at residue 187. We found the same mutation in a Dutch family but a Danish FAF family had a G654T mutation, predicting Asp to Tyr at residue 187. We also found the G654T transversion in a Czech family. Using GSN polymorphisms, different haplotypes were found in the Danish and Czech families. We conclude that substitution of the uncharged Asn or Tyr for the acidic Asp at residue 187 creates a conformation that may be preferentially amyloidogenic for GSN.

Alleles↗