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G Dawson

Publications and source records attributed to G Dawson.

At least 145 records · Page 8Linked to original sources
PubMed1991

Synthesis and processing of lysosomal alpha-fucosidase in cultured human fibroblasts.

The lysosomal enzyme alpha-L-fucosidase from human skin fibroblasts is synthesized as a 53 kDa glycosylated precursor which is then proteolytically processed to a 50 kDa mature form. This was confirmed by pulse-chase labeling studies with chase times up to 72 h. In fibroblasts treated with 1-deoxymannojirimycin to prevent trimming of high mannose oligosaccharides, endoglycosidase H (endo H) treatment completely deglycosylated and reduced the size of immunoprecipitated alpha-fucosidase by 4-5 kDa, suggesting the presence of two oligosaccharide units. Endoglycosidase H and endo F studies on untreated alpha-fucosidase suggested the presence of one complex-type and one high mannose-type unit, and that the final processing from 53 to 50 kDa did not involve the removal of carbohydrate. Processing was inhibited by the thiol proteinase inhibitor Ep-459, but not by Ep-475 or leupeptin. Since Ep-459 treatment increased both alpha-fucosidase activity (3-fold) and the amount of immunoprecipitable alpha-fucosidase protein in normal human skin fibroblasts, this suggests a role for cysteine-like proteinases either directly or indirectly in lysosomal hydrolase processing and turnover. Subcellular fractionation studies revealed that the proteolytic processing of the 53 kDa precursor to the 50 kDa mature form occurred in the lysosome, or some other dense organelle.

Cell Compartmentation↗
PubMed1991

Seroprevalence of HTLV-I/II and HIV-1 infection among male intravenous drug abusers in Chicago.

We surveyed for serologic evidence of either HIV-1 or HTLV-I/II infection in 387 male veterans who entered into an inpatient drug treatment center. Serum was obtained after receiving written informed consent. Serum specimens were tested by enzyme-linked immunosorbent assay for antibody to HIV-1 and for antibody to HTLV-I/II; sera that were repeatedly reactive were then tested by Western blot (HIV-1/HTLV-I/II) and radioimmunoprecipitation assay (HTLV-I/II). Sixty-five of 387 (16.79%) patients were tested and confirmed as positive for HTLV-I/II only antibodies and 30 of the 387 (7.75%) were positive for HIV-1 only antibodies. An additional nine patients (2.32%) were seropositive for antibodies to both viruses. A statistically significant difference in the CD4/CD8 lymphocyte ratio was associated with HIV-1 seropositivity. HTLV-I/II seropositivity was strongly associated with black race, age, and duration of i.v. drug use, but not with sexual intercourse as determined by lifetime history of number of sexual partners, incidence of sexually transmitted diseases, type of drug used, or needle-sharing practices.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Acylation of exogenous glycosylsphingosines by intact neuroblastoma (NCB-20) cells.

Acylation of exogenously added galactosylsphingosine was demonstrated in intact NCB-20 neuroblastoma cells, a cell line that normally does not synthesize galactosylceramide. Labeling of cells with [3H]palmitic acid for 6 h in the presence of 100 microM exogenous galactosylsphingosine (GalSph) resulted in a more than 3-fold increase in the incorporation of label into the ceramide monohexoside fraction relative to controls. This increase, which was almost entirely due to the incorporation of labeled nonhydroxy fatty acid into galactosylceramide, was linear over a concentration range of 1-100 microM galactosylsphingosine and for the first 5 h after the addition of galactosylsphingosine. Similarly, the addition of 100 microM glucosylsphingosine resulted in a 3-fold increase of label incorporated into glucosylceramide. Incubation of cells with 100 microM GalSph and labeled fatty acids of various chain lengths revealed that the acylation of GalSph was specific for medium chain (C16-C18) nonhydroxy fatty acids, suggesting that this was an enzyme-mediated reaction. The enzymatic nature of GalSph acylation was further demonstrated when cells were incubated for 72 h with 15 microM [3H]galactosylsphingosine labeled in the galactose moiety. [3H]Galactosylceramide containing only medium chain non-hydroxy fatty acids accumulated linearly with time reaching a maximum at 48 h and was observed to be further metabolized to ceramide dihexoside. This acylation reaction may be potentially important for the removal of glycosylsphingosines in the cell.

Acylation↗
PubMed1990

Progressive hypoxia inhibits the de novo synthesis of galactosylceramide in cultured oligodendrocytes.

Neonatal rat oligodendrocyte (OLG) cultures exposed to 6 h of gradual, progressive hypoxia in a GasPak (BBL, Becton Dickinson) apparatus were not injured or metabolically impaired, but instead showed a specific inhibition of de novo synthesis (measured by [3H]palmitic acid labeling) of the major myelin component galactosylceramide (GalCer). De novo synthesis of the 2-hydroxy fatty acid GalCer (HFA-GalCer) species, which requires O2 for its synthesis, was most severely inhibited (by 65%), while non-hydroxy GalCer species (NFA-GalCer) were less affected. The synthesis of membrane glycerophospholipids and sphingomyelin was unaffected by hypoxia. Treatment of OLG with 12 nM oligomycin, an inhibitor of mitochondrial ATP synthesis, resulted in an inhibition (by 50-60%) of synthesis of all GalCer species. [3H]Palmitate labeling of NFA-ceramide, the ungalactosylated precursor of NFA-GalCer species, increased in both hypoxia and oligomycin treatments, suggesting that the conversion of newly synthesized ceramide to GalCer was blocked. Newly synthesized HFA-ceramide did not accumulate in OLG, but the small labeled HFA-ceramide pool present during hypoxia was not converted into HFA-GalCer. Pulse-chase studies indicated that NFA- and HFA-ceramides labeled during these treatments were available for galactosylation and could be converted into GalCer upon reoxygenation. [3H]Galactose labeling of NFA-GalCer species was enhanced 2-fold in hypoxia, in contrast to the inhibition seen with [3H]palmitic acid labeling. Thus, while de novo GalCer synthesis was blocked in hypoxia, galactosylation of pre-existing ceramide pools was actually enhanced. Our evidence suggests that hypoxia results in a reversible inhibition of transport of newly synthesized ceramide from its site of synthesis to its site of galactosylation, but causes an increase in galactosylation of subcellular pools of pre-existing ceramide.

Animals↗
PubMed1990

Asymmetric extraction of membrane lipids by CHAPS.

We have characterized and quantitated the lipids which are cosolubilized with serotonin 5-HT1A sites from sheep brain using 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS). Dialysis of the CHAPS extract produced a [3H]8-hydroxy(2-di-n-propylamino)tetralin [( 3H]8-OH-DPAT) binding vesicular preparation of the protein. Quantitative analysis of the lipids present in the CHAPS extract by HPTLC and transmittance-densitometry revealed extraction of phosphatidylethanolamine (PE), phosphatidylcholine (PC), phosphatidylinositol (PI), phosphatidyl serine (PS) and phosphatidic acid (PA) in striking preference over cholesterol, galactosylceramides, sulfatides and sphingomyelin. All lipids present in the clear CHAPS-extract were coeluted with the [3H]8-OH-DPAT binding preparation were separated by centrifugation, 95-100% of the [3H]8-OH-DPAT binding protein was retained in the vesicle-containing pellet. The supernatant contained small amounts of cholesterol, PE and PC, but virtually no PS, PI, or PA, whereas the vesicular pellet contained all the lipids mentioned, indicating that PS, PI and PA are more tightly bound to the vesicles than PE, PC and cholesterol. SDS-PAGE analysis of the pellet revealed two major protein bands, at 58 kDa and 33.5 kDa, respectively. Our report outlines a simple and improved densitometric assay used for the first detailed analysis of lipids cosolubilized with an active, membrane protein, and also, a simple assay for CHAPS.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1990

Phospholipase C activity in NCB-20 cells is inhibited by protein kinase A-mediated phosphorylation of low molecular mass GTP-binding proteins.

We have previously shown that bradykinin-induced production of second messengers such as inositol trisphosphate and diacylglycerol in neurotumor cells is inhibited by raising cellular cyclic AMP levels, which in turn inhibit phospholipase C. A monoclonal antibody to phospholipase C-II immunoprecipitated the 140-kDa form of phospholipase C-II from [35S]methionine/[3H]eucine-labeled cells, but not [32P]orthophosphate-labeled phospholipase C-II, following treatment with either forskolin or dibutyryl cyclic AMP. This suggested that phospholipase C is not the target for cyclic AMP-dependent protein kinase-mediated phosphorylation. In vitro studies confirmed that phospholipase C activity was inhibited by raising cellular cAMP levels, and partial sensitivity to Bordetella pertussis toxin suggested the involvement of a GTP-binding protein which could be the target for protein kinase A. The involvement of a GTP-binding protein in coupling the bradykinin receptor to phospholipase C was further suggested by the ability of both guanosine 5'-O-(thio-triphosphate) and fluoride (NaF) to release inositol phosphates from NCB-20 cell membranes previously labeled with [3H]inositol. Both effects were blocked by pretreatment of the cells with protein kinase A activators, further suggesting a GTP-binding protein as the target for protein kinase A-mediated phosphorylation. When whole NCB-20 cell extracts were blotted onto nitrocellulose and incubated with [alpha- 32P]GTP, a major 24-kDa band plus minor bands at 22 and 20 kDa were revealed by autoradiography. A pH 3.0/6.0 soluble (basic protein) NCB-20 cell extract revealed the major 24-kDa band plus the 20-kDa band, and similar basic proteins were shown to be heavily phosphorylated following [32P]orthophosphate labeling and pretreatment with forskolin. The size and ability to bind GTP on Western blots are characteristic of the ras, rho, smg, etc. family of GTP-binding proteins recently suggested to be the much sought after GPLC (Lapetina, E.G., Lacal, J. C., Reep, B. R., and Molina y Vedia, L. (1989) Proc. Natl. Acad. Sci. U.S.A. 86, 3131-3134; Wang, P., Nishihata, J., Takabori, E., Yamamoto, K., Toyoshima, S., and Osawa, T. (1989) J. Biochem. (Tokyo) 105, 461-466; Nagata, K.-I., Nagao, S., and Nozawa, Y. (1989) Biochem. Biophys. Res. Commun. 160, 235-242). We propose that GPLC is uniquely sensitive to protein kinase A-mediated phosphorylation and that phosphorylation inhibits stimulus-secretion coupling in these cells.

1-Methyl-3-isobutylxanthine↗
PubMed1990

Polyclonal IgM anti-GM1 ganglioside antibody in patients with motor neuron disease and variants.

Recent studies reported the presence of anti-ganglioside antibodies in occasional patients with motor neuron disease. We found polyclonal serum IgM anti-GM1 antibodies by an anti-GM1 enzyme-linked immunosorbent assay (ELISA) in 9 (19%) of 48 patients with motor neuron disease. A comparable frequency of IgM anti-GM1 antibodies was found in 4 (10%) of 40 sera from patients with other neurological disease. Three (17%) of 18 sera from the patients with motor neuron disease and 2 (17%) of 12 sera from patients with other neurological diseases had anti-GM1 immunostaining as shown by thin layer chromatography immunoblot. One patient with a lower motor neuron variant of motor neuron disease or motor axonopathy without multifocal conduction block had a markedly elevated polyclonal IgM anti-GM1 ELISA titer (greater than 1:64,000) with prominent immunostaining of GM1, moderate immunostaining of GM2, and weak and inconsistent immunostaining of GD1b by thin layer chromatography immunoblot. Treatment with prednisone resulted in clinical improvement despite increasing anti-GM1 antibody titers. These data indicate that patients with motor neuron disease have measurable levels of anti-ganglioside antibodies as frequently as patients with other neurological diseases. This contrasts with a small subgroup of patients with a lower motor neuron variant of motor neuron disease or motor axonopathy who have markedly elevated levels of serum anti-ganglioside antibodies and a clinical syndrome that is treatable with immunosuppression.

Amyotrophic Lateral Sclerosis↗
PubMed1990

Affective exchanges between young autistic children and their mothers.

This study examined autistic children's social behavior, affect, and use of gaze during naturalistic interactions with their mothers. Sixteen autistic children, 30 to 70 months of age, and 16 normal children, matched on receptive language, participated. Children and their mothers were videotaped during three situations: a free-play period, a more structured period during which communicative demand was made on the child, and a face-to-face interaction. In all three situations, autistic and normal children did not differ in the frequency or duration of gaze at mother's face. In the one condition (face-to-face interaction) during which affective expressions were coded, autistic and normal children also were not found to differ significantly in the frequency or duration of smiles displayed, and neither group displayed frowns. However, autistic children were much less likely than normal children to combine their smiles with eye contact in a single act that conveyed communicative intent. Autistic and normal children were not found to differ in the percentages of smiles they displayed to social versus nonsocial events. However, when autistic children's responses to mother's smiles specifically were examined, it was found that they were much less likely to smile in response to mother's smiles than were normal children. Finally, it was found that mothers of autistic children displayed fewer smiles and were less likely to smile in response to their children's smiles, when compared with mothers of normal children. These findings suggest that the autistic child's unusual affective behavior may negatively affect the behavior of others.

Affect↗
PubMed1990

The effect of interleukin 4 (BSF-1) on infection of peripheral blood monocyte-derived macrophages with HIV-1.

The effects of various cytokines were examined in an in vitro model of human immunodeficiency virus type 1 (HIV-1) infection of human peripheral blood monocyte-derived macrophages (MDM). Monocytes were obtained from blood of normal donors by Ficoll/hypaque gradient centrifugation and adherence. These cells were allowed to mature in the presence of varying concentrations of cytokines. After five days in culture, cells were harvested, counted, and inoculated with S5G7, an HTLV-IIIB subclone. The cells were replated in the presence of the same concentrations of cytokines. Culture supernatants were sampled over 28 days for p24 antigen (Ag) as measured by Ag capture assay. In repeat experiments, the following observations were made: 1. MDM from some donors could be infected only in the presence of tumor necrosis factor-alpha (TNF-alpha), granulocyte/macrophage colony-stimulating factor (GM-CSF) or interleukin 4 (IL-4); 2. The effect of GM-CSF was variable; TNF alpha also enhanced HIV replication above controls; 3. IL-4 was the most potent enhancer of HIV-1 replication in MDM of the cytokines tested, inducing p24 Ag levels 75-230 times those seen in control cultures run simultaneously. This effect was dose dependent. Ag production was not observed until Day 14 postinfection in most experiments. Multinucleated giant cell formation was observed only in the presence of IL-4.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Preferential inhibition of lysosomal beta-mannosidase by sucrose.

The lysosomal storage disease beta-mannosidosis, described in both goats and humans, can be detected by measuring a deficiency in hydrolysis of the fluorogenic substrate 4-methylumbelliferyl-beta-D-mannoside. An inhibitor of guinea pig beta-mannosidase (beta-man) activity was detected when tissue was homogenized in phosphate-buffered-saline (pH 7.4) containing 0.25 mol/l sucrose. The existence of such an inhibitor was apparent when the enzyme was immunoprecipitated from tissue using a specific beta-man polyclonal antibody. There was up to a threefold increase in activity in the immunoprecipitated enzyme (antibody-enzyme complex) compared to the activity of the nonimmunoprecipitated enzyme. An extensive study was therefore undertaken to determine the nature and specificity of this inhibitor by analyzing the effect of a range of metal ions and sugars on beta-man activity compared to other lysosomal hydrolase activities. Although ferrous, ferric, cobalt, and manganese ions were highly inhibitory to beta-man, they also inhibited other lysosomal hydrolases to a similar extent. Likewise, mannose inhibited both alpha- and beta-man activities equally. The only compound to specifically inhibit beta-man in a manner similar to that observed in the tissue homogenate was glucosyl(beta, 2)fructofuranoside (sucrose). This is an important finding in that tissue samples are commonly prepared in buffers containing sucrose and this could lead to a wrong diagnosis of beta-man deficiency. In order to determine if the absence of an activator factor or alternatively the presence of a specific inhibitor was a contributing factor in the lack of beta-man activity in cultured fibroblasts from affected humans and goats, mixing studies with normal and affected cell extracts were performed but no restoration or inhibition of beta-man activity was found.

Animals↗
PubMed1989

Rapid dephosphorylation of protein kinase C substrates by protein kinase A activators results from inhibition of diacylglycerol release.

The biochemical events encompassing the dephosphorylation of protein kinase C substrates by protein kinase A activators have been investigated in a neurotumor cell line, NCB-20. Treatment of [32P]orthophosphate-labeled cells with protein kinase A activators (e.g. forskolin, dibutyryl cAMP, prostaglandin E1) resulted in an inhibition of protein kinase C activity due to a failure of the protein kinase C complex to translocate into the membrane. Phospholipase C activity, as measured by the synchronous release of diacylglycerol and inositol phosphates (inositol 1,4,5-trisphosphate, inositol 1,4-bisphosphate, and inositol 1-phosphate) in response to bradykinin, was inhibited up to 50% following exposure to protein kinase A activators. At the same time, phospholipase C-specific inositol phospholipid substrates (phosphatidylinositol, phosphatidylinositol 4-phosphate, and phosphatidylinositol 4,5-bisphosphate) were found to accumulate in NCB-20 cells following treatment with protein kinase A activators. This suggests that phospholipase C may be altered through protein kinase A-mediated protein phosphorylation. Second messenger generation (inositol phosphates, diacylglycerol, and Ca2+) is therefore inhibited through cyclic AMP-mediated shutdown of the inositol lipid cycle at the level of phospholipase C.

1-Methyl-3-isobutylxanthine↗
PubMed1989

Phosphorylation of myelin basic protein in intact oligodendrocytes: inhibition by galactosylsphingosine and cyclic AMP.

We have previously shown that cyclic AMP (cAMP) inhibits the protein kinase C (PKC)-mediated phosphorylation of myelin basic protein (MBP) in cultured oligodendrocytes (OLGs). Recently, it has been demonstrated that the long chain base sphingosine inhibits PKC by competing PKC effectors (diacylglycerol and phorbol esters) for a binding site on the kinase (Hannun and Bell: Science 235: 670-674, 1987). In this report we define further the mechanism by which cAMP inhibits MBP phosphorylation by comparing the effects of cAMP with that of galactosylsphingosine (psychosine), a potential catabolite of galactocerebroside, the major OLG glycosphingolipid. We identify the consequences of psychosine treatment and PKC down-regulation on OLG morphology and electrophysiology and discuss their relevance. Our results in intact ovine oligodendrocytes are consistent with a mechanism in which cAMP inhibits MBP phosphorylation by interfering with the release of diacylglycerol (DAG) from phosphatidylinositol. First, the effects of cAMP on MBP phosphorylation are reversed with exogenous TPA; and second, cAMP inhibits the incorporation of 1-[14C]arachidonate into DAG and specifically inhibits the turnover (as judged by 32PO4 3-incorporation) of phosphatidylinositol. Psychosine inhibits MBP phosphorylation, and its action can be reversed by TPA suggesting a mechanism of inhibition similar to that described for other systems. In addition, psychosine has profound effects on OLG morphology; it disintegrates OLG processes while leaving the cell soma intact. Stable hyperpolarized resting potentials were obtained following psychosine treatment, but there was a 66% decrease in membrane capacitance indicating a significant decrement in membrane surface area. The morphological changes induced by psychosine are reversible and can be eliminated by removing the drug but not by the addition of TPA. Whether inhibition of PKC by psychosine plays any role in process dissolution remains an unanswered question. However, current evidence suggests that a PKC-independent mechanism may be at play. This investigation in conjunction with our previous work emphasizes a role for the interregulation of protein kinase A (PKA) and PKC in the control of OLG somal vs. myelin components. This may have significant implications for central nervous system myelin assembly.

Animals↗
PubMed1989

Differential regulation of basic protein phosphorylation by calcium phospholipid and cyclic-AMP-dependent protein kinases.

Myelin basic protein, an 80-kilodalton (kDa) protein in rat oligodendrocytes, and an 80-kDa basic protein in neuroblastoma x neonatal Chinese hamster brain explant hybrids were phosphorylated extensively when the cells were treated with either phorbol esters (TPA) or diacylglycerols (e.g., oleyoyl-acetylglycerol). TPA-stimulated phosphorylation was inhibited by pre-incubation with 50 microM psychosine (galactosyl-sphingosine), confirming that it is mediated through the phospholipid-dependent protein kinase C (PK-C). Surprisingly, phosphorylation of these proteins was inhibited by incubation of cells with agents which result in activation of cyclic-AMP-dependent protein kinase (dibutyryl cyclic AMP or forskolin). In contrast, phosphorylation of other nonbasic proteins, for example, the oligodendrocyte-specific 2',3'-cyclic nucleotide phosphohydrolase, was stimulated under these conditions (Vartanian et al.: Proceedings of the National Academy of Sciences of the United States of America 85:939, 1988). The possible role of cyclic AMP in activating specific phosphatases or restricting the availability of diacylglycerol for PK-C activation is discussed.

Animals↗
PubMed1989

Phospholipases and the molecular basis for the formation of ceroid in Batten disease.

Lysosomal ceroid/lipofuscinosis storage in human, canine, and ovine forms of neuronal ceroidlipofuscinosis is predominantly in neurons and retinal pigment epithelial cells. Despite problems in identifying individual storage materials, it is believed that non-enzymic oxidation of unsaturated fatty acids in phospholipids and inhibition of lysosomal proteolysis, leading to massive deposition of autofluorescent pigment, is the cause of the disease. We have, therefore, studied cellular phospholipases and find a marked deficiency of lysosomal phospholipase A1 (PLA1) in canine NCL brain. Other lysosomal hydrolases, and cytosolic/mitochondrial forms of phospholipase A2 are completely normal. We believe that the PLA1 deficiency leads to transient lysosomal storage of phospholipids containing peroxy fatty acids which are then chemically converted to hydroxynonenal, a potent inhibitor of a thiol-dependent enzymes. Inhibition of proteases is believed to be intrinsic to the formation of lipofuscin. An inherited deficiency of a thiol protease (the lysosomal cathepsin H) in two siblings with NCL can also lead to build up of peptides which are then cross-linked and converted into ceroid-containing curvilinear bodies. Thus there is evidence for molecular and genetic heterogeneity in Batten disease.

Animals↗
PubMed1989

A comparison of hemispheric asymmetries in speech-related brain potentials of autistic and dysphasic children.

In a previous study (G. Dawson, C. Finley, S. Phillips, & L. Galpert, 1986, Child Development, 57, 1440-1453) it was found that measures of hemispheric asymmetry during speech processing were predictive of level of language ability in autistic children. The purpose of the present study was to determine whether a similar relationship between pattern of hemispheric asymmetry and language ability exists for language-impaired children without autism. Ten autistic children (8-13 years), 10 dysphasic children (6-15 years), and 10 normal children (8-13 years) were compared in terms of their patterns of hemispheric asymmetry in the averaged cortical evoked response to a simple speech stimulus, and the relationship between pattern of hemispheric asymmetry and language ability was assessed for each clinical group. It was found that, for both the autistic and dysphasic groups, the majority of subjects showed a reversed direction of hemispheric asymmetry from that characteristic of the normal group. A strong relationship between pattern of asymmetry and level of language ability was found for autistic subjects; autistic subjects with more severe language impairments were more likely to show reversed asymmetry than subjects with less severe language impairments. In contrast, no relationship between language ability and direction of hemispheric asymmetry in the evoked response was found for dysphasic subjects. Separate analyses of right and left hemisphere evoked responses indicated that language ability was related to right hemisphere activity for autistic subjects, and to left hemisphere activity for dysphasic subjects.

Adolescent↗
PubMed1989

Bradykinin analogs antagonize bradykinin-induced second messenger production in a sensory neuron cell line.

Bradykinin is the prime initiator of pain and the key initial activator of the inflammatory response at the site of tissue injury. The subsequent transfer of nociceptive information (pain sensation) into the central nervous system is then mediated via afferent type C dorsal root ganglion neurons. A recently developed hybrid cell line, F-11, shows many qualities characteristic of these pain-sensitive cells. In these neuronal hybrids, we have found that bradykinin induces sequential elevation in the concentrations of several second messengers involved in neuronal activation, including inositol trisphosphate (6.5-fold), intracellular calcium (2.7-fold), and cyclic GMP (20.5-fold). Importantly, the production of these second messengers is potently inhibited by several novel bradykinin antagonists that possess no intrinsic agonist activity. The same relative rank order of potency of inhibition of bradykinin-induced second messenger production was achieved in the inositol trisphosphate, calcium, and cyclic GMP assay systems, suggesting strongly that all three messenger systems are being activated by the same bradykinin receptor. The most potent antagonist was D-Arg0-Hyp3-Thi5,8-D-Phe7-bradykinin, which inhibited in a competitive manner, with pA2 values, upon Schild plot analysis, in the nanomolar range. These potent bradykinin antagonists may be useful in the characterization of bradykinin receptors and in the clinical management of pain and inflammation.

Animals↗