Biomedical subjects

E Weber

Publications and source records attributed to E Weber.

At least 127 records · Page 7Linked to original sources

PubMed1997

Assessment and management of urinary incontinence among homebound older adults: a clinical trial protocol.

Urinary incontinence is a common and costly problem among homebound older adults. This article describes the assessment and management protocols utilized in a clinical trial examining the effectiveness of behavioral interventions in treating urinary incontinence in homebound older adults. Individuals with urinary incontinence were identified and referred to the study by home care nurses from two large home health agencies. Following in-home assessment, eligible subjects were randomized to an immediate treatment group or a delayed treatment group (control group). Subjects who were cognitively intact were treated with biofeedback-assisted pelvic floor muscle training, while subjects with cognitive impairments were treated with a program of prompted voiding. Two nurse practitioners assessed and treated subjects participating in the study.

Aged↗

PubMed1996

Attenuation of nociceptive responses by ACEA-1021, a competitive NMDA receptor/glycine site antagonist, in the mice.

Intrathecal administration of N-methyl-D-aspartate (NMDA) and non-NMDA receptor antagonists has been shown to produce antinociception in various animal models of pain. In the present study we examined the effect of 5-nitro-6,7-dichloro-1,4-dihydro-2,3-quinoxalinedione (ACEA-1021), a competitive NMDA receptor/glycine site antagonist, on nociceptive responses in the tail flick and formalin tests in mice. Swiss Webster mice were injected with ACEA-1021 intraperitoneally (1-60 mg/kg), or intrathecally (1-40 micrograms/mouse), and tested for antinociception. Systemic administration of ACEA-1021 attenuated the nociceptive responses solely in the formalin test. Nevertheless, intrathecal administration of ACEA-1021 showed equally potent attenuation of nociceptive responses in both animal models of pain. The effect of ACEA-1021 was also examined on caudally directed biting and scratching (CDBS) behaviors induced by intrathecal administration of NMDA. Microinjections of NMDA (1-1000 microM) in the spinal cord produced dose-dependent CDBS behaviors. Mice pretreated with ACEA-1021 (0.5-40 micrograms/mouse) showed dose-dependent protection against CDBS behaviors induced by intrathecal NMDA. Taken together, the results suggest that ACEA-1021 may block spinal NMDA receptors to attenuate nociceptive responses, however, our data cannot exclude the involvement of non-NMDA receptors.

Animals↗

PubMed1996

Analogs of 3-hydroxy-1H-1-benzazepine-2,5-dione: structure-activity relationship at N-methyl-D-aspartate receptor glycine sites.

A series of aromatic and azepine ring-modified analogs of 3-hydroxy-1H-1-benzazepine-2,5-dione (HBAD) were synthesized and evaluated as antagonists at NMDA receptor glycine sites. Aromatic ring-modified HBADs were generally prepared via a Schmidt reaction with substituted 2-methoxynaphthalene-1,4-diones followed by demethylation. Electrophilic aromatic substitution of benzazepine 3-methyl ethers gave 7-substituted analogs. The preparation of multiply substituted 2-methoxynaphthalene-1,4-diones was effected via Diels-Alder methodology utilizing substituted butadienes with 2-methoxybenzoquinones followed by aromatization. Structural modifications, such as elimination of the aromatic ring, removal of the 3-hydroxyl group, and transfer of the hydroxyl group from C-3 to C-4, were also studied. An initial evaluation of NMDA antagonism was performed using a [3H]MK801 binding assay. HBADs demonstrating NMDA antagonist activity as indicated by inhibition of [3H]MK801 binding were further evaluated employing a [3H]-5,7-dichlorokynurenic acid (DCKA) glycine site binding assay. Selected HBADs were characterized for functional antagonism of NMDA and AMPA receptors using electrophysiological assays in Xenopus oocytes and cultured rat cortical neurons. Antagonist potency of HBADs showed good correlation between the different assay systems. HBADs substituted at the 8-position possessed the highest potency with the 8-methyl (5), 8-chloro (6), and 8-bromo (7) analogs being the most active. For HBAD 6, the IC50 in [3H]-DCKA binding assays was 0.013 microM and the Kb values for antagonism of NMDA receptors in oocytes (NR1a/2C) and cortical neurons were 0.026 and 0.048 microM, respectively. HBADs also antagonized AMPA-preferring non-NMDA receptors expressed in oocytes but at a lower potency than corresponding inhibition of NMDA receptors. HBADs demonstrating a high potency for NMDA glycine sites showed the highest steady-state selectivity index relative to AMPA receptors. Substitution at the 6-, 7-, and 9-positions generally reduced or eliminated glycine site affinity. Moving the hydroxyl group from C-3 to C-4 reduced receptor affinity, and potency was eliminated by the removal of the aromatic ring or the hydroxyl group. These data indicate that the HBAD series has specific structural requirements for high receptor affinity. With the exception of substitution at C-8, modified HBADs generally have a lower affinity at NMDA receptor glycine sites than the parent compound 3. Mouse maximum electroshock-induced seizure studies show that the three HBADs selected for testing have in vivo potency with the 6,8-dimethyl analog (52) being the most potent (ED50 = 3.9 mg/kg, iv).

Animals↗

PubMed1996

Structure-activity relationships of 4-hydroxy-3-nitroquinolin-2(1H)-ones as novel antagonists at the glycine site of N-methyl-D-aspartate receptors.

A series of 4-hydroxy-3-nitroquinolin-2(1H)-ones (HNQs) was synthesized by nitration of the corresponding 2,4-quinolinediols. The HNQs were evaluated as antagonists at the glycine site of NMDA receptors by inhibition of [3H]DCKA binding to rat brain membranes. Selected HNQs were also tested for functional antagonism by electrophysiological assays in Xenopus oocytes expressing either 1a/2C subunits of NMDA receptors or rat brain AMPA receptors. The structure-activity relationships (SAR) of HNQs showed that substitutions in the 5-, 6-, and 7-positions in general increase potency while substitutions in the 8-position cause a sharp reduction in potency. Among the HNQs tested, 5,6,7-trichloro HNQ (8i) was the most potent antagonist with an IC50 of 220 nM in [3H]DCKA binding assay and a Kb of 79 nM from electrophysiological assays. Measured under steady-state conditions HNQ 8i is 240-fold selective for NMDA over AMPA receptors. The SAR of HNQs was compared with those of 1,4-dihydroquinoxaline-2,3-diones (QXs) and 1,2,3,4-tetrahydroquinoline-2,3,4-trione 3-oximes (QTOs). In general, HNQs have similar potencies to QXs with the same benzene ring substitution pattern but are about 10 times less active than the corresponding QTOs. HNQs are more selective for NMDA receptors than the corresponding QXs and QTOs. The similarity of the SAR of HNQs, QXs, and QTOs suggested that these three classes of antagonists might bind to the glycine site in a similar manner. With appropriate substitutions, HNQs represent a new class of potent and highly selective NMDA receptor glycine site antagonists.

Animals↗

PubMed1996

Pharmacology of ACEA-1416: a potent systemically active NMDA receptor glycine site antagonist.

Excitatory amino acid receptor antagonists show potential for the treatment of ischemic stroke and head trauma. In search of novel antagonists, a series of alkyl- and alkoxyl-substituted 1, 4-dihydro-2,3-quinoxalinediones were synthesized and assayed for inhibition of glutamate receptors. We report on the pharmacological characterization of one such compound, 7-chloro-6-methyl-5-nitro-1,4-dihydro-2, 3-quinoxalinedione (ACEA-1416). Electrophysiological assays showed that ACEA-1416 is a potent antagonist of rat brain NMDA receptors expressed in Xenopus oocytes, and NMDA receptors expressed by cultured rat cortical neurons. Antagonism is via competitive inhibition at glycine co-agonist sites (Kb = 7.9 nM in oocytes, Kb = 11 nM in neurons). ACEA-1416 also antagonizes AMPA receptors, though potency is considerably lower (Kb = 3.5 microM in oocytes, Kb = 1.6 microM in neurons). Oocyte assays indicated that ACEA-1416 is weak or inactive as an antagonist at NMDA receptor glutamate binding sites (Kb > 5.9 microM) and metabotropic glutamate receptors (Kb > 57 microM). Many NMDA receptor glycine site antagonists show poor penetration of the blood-brain barrier. Systemic bioavailability of ACEA-1416 was assessed by measuring the ability of the compound to protect against electroshock-induced seizures in mice. Protective effects of ACEA-1416 had rapid onset following i.v. administration. Peak efficacy was at approximately 2 min and the biological half-time of protection was approximately 60 min. The ED50 measured at peak efficacy was approximately 1.5 mg/kg. Our results show that ACEA-1416 is a high potency systemically active NMDA receptor glycine site antagonist and a moderate potency AMPA receptor antagonist. Separate studies indicate that ACEA-1416 is efficacious as a neuroprotectant in a rat model of focal cerebral ischemia. Taken together, our results suggest that ACEA-1416 has potential for clinical development as a neuroprotectant.

Animals↗

PubMed1996

Inhibition of morphine tolerance by NMDA receptor antagonists in the formalin test.

5-Nitro-6,7-dimethyl-1,4-dihydro-2,3-quinoxalinedione (ACEA-1328) was characterized in vitro for antagonism of excitatory amino acid receptors, and subsequently tested in vivo and compared with MK-801 for phencyclidine (PCP)-like motor stimulation, antinociception, and effects on morphine tolerance in mice. Assayed on rat cerebral cortical glutamate receptors expressed in Xenopus oocytes ACEA-1328 showed potent (Kb approximately 40 nM) antagonism at NMDA receptor/glycine sites and moderate (Kb approximately 3 microM) antagonism at non-NMDA receptors. In both cases inhibition was predominantly competitive. ACEA-1328 was weak, or inactive, at NMDA receptor glutamate recognition sites, metabotropic receptors and opioid binding sites. In the formalin and rotarod tests ACEA-1328 and MK-801 produced both antinociception and disturbances of motor coordination. MK-801 caused a PCP-like motor stimulatory effect, whereas ACEA-1328 was devoid of such an effect. In tolerance studies, ACEA-1328 and MK-801 each blocked morphine tolerance in the formalin test, the effect of ACEA-1328 was dose-dependent. Our data contribute to a growing body of evidence which suggests that activation of NMDA receptors is critical for the development of opioid tolerance, and that antagonism at NMDA receptor/glycine sites may have potential as a means of diminishing tolerance with no PCP-like motor stimulatory side effects.

Animals↗

PubMed1996

The neuroprotective efficacy of MK-801 in focal cerebral ischemia varies with rat strain and vendor.

The present study was designed to evaluate whether the neuroprotective efficacy of MK-801 in focal cerebral ischemia was dependent on strain and/or vendor differences. MK-801 (0.12 mg/kg i.v. bolus followed by 0.108 mg/kg/h infusion or 0.60 mg/kg i.v. bolus followed by 0.540 mg/kg/h infusion) or saline was administered just after intraluminal middle cerebral artery occlusion. Administration of 0.540 mg/kg/h MK-801 provided strain/line-dependent neuroprotection in the following rank order: Simonsen Laboratories Sprague-Dawley rats > Simonsen Laboratories Wistar rats > Taconic Laboratories Sprague-Dawley rats. After 0.108 mg/kg/h MK-801 treatment, Simonsen Laboratories Wistar rats were the only strain/line that were significantly neuroprotected. These results indicate that the neuroprotective effect of an experimental drug may be influenced by rat strain and vendor differences.

Animals↗

PubMed1996

Glioma cells induce gamma-glutamyl transpeptidase activity in cultured blood but not lymphatic endothelial cells.

Glial cells have been shown to induce enzyme activities, which are characteristically high in brain capillaries, in cerebral and non cerebral endothelial cells in culture. We evaluated the activity of gamma-glutamyl transpeptidase (gamma GT) in freshly isolated (ex vivo) bovine blood (BEC) and lymphatic (LEC) endothelial cells. We also tested the effect of C6 glioma cell conditioned medium (GCM) on gamma GT activity of BEC and LEC in primary culture. Ex vivo BEC had a high gamma GT activity, only 9% of which was retained in culture. After exposure to GCM, however, gamma GT activity of cultured BEC was twofold higher than with control medium. By contrast gamma GT activity was extremely low in ex vivo LEC and did not significantly increase in cultured LEC exposed to GCM. These data show that the basal levels of gamma GT are markedly different in BEC and LEC and also that, unlike BEC, LEC are not capable of producing more gamma GT in response to glial stimulation.

Animals↗

PubMed1996

Synthesis and structure-activity relationships of 1,2,3,4-tetrahydroquinoline-2,3,4-trione 3-oximes: novel and highly potent antagonists for NMDA receptor glycine site.

A series of 1,2,3,4-tetrahydroquinoline-2,3,4-trione 3-oximes (QTOs) was synthesized and evaluated for antagonism of NMDA receptor glycine site. Glycine site affinity was determined using a [3H]DCKA binding assay in rat brain membranes and electrophysiologically in Xenopus oocytes expressing 1a/2C subunits of cloned rat NMDA receptors. Selected compounds were also assayed for antagonism of AMPA receptors in Xenopus oocytes expressing rat brain poly-(A)+RNA. QTOs were prepared by nitrosation of 2,4-quinolinediols. Structure-activity studies indicated that substitutions in the 5-, 6-, and 7-positions increase potency, whereas substitution in the 8-position causes a decrease in potency. Among the derivatives evaluated, 5,6,7-trichloro-QTO was the most potent antagonist with an IC50 of 7 nM in the [3H]DCKA binding assay and a Kb of 1-2 nM for NMDA receptors expressed in Xenopus oocytes. 5,6,7-Trichloro-QTO also had a Kb of 180 nM for AMPA receptors in electrophysiological assays. The SAR of QTOs was compared with the SAR of 1,4-dihydroquinoxaline-2,3-diones (QXs). For compounds with the same benzene ring substitution pattern, QTOs were generally 5-10 times more potent than the corresponding QXs. QTOs represent a new class of inhibitors of the NMDA receptor which, when appropriately substituted, are among the most potent glycine site antagonists known.

Animals↗

PubMed1996

Distinct functional properties of Rab3A and Rab3B in PC12 neuroendocrine cells.

Rab3A and Rab3B are highly homologous monomeric GTPases that are putative regulators of exocytosis in those tissues in which they are expressed. We have characterized and directly compared the targeting and functional properties of these isoforms in PC12 neuroendocrine cells. Rab3A and Rab3B both targeted to norepinephrine (NE)-containing large dense core vesicles (LDCVs) when stably expressed in PC12 cells, as determined by immunofluorescence and membrane fractionation. Both Rab3 isoforms also bound to recombinant rabphilin-3A in a GTP-dependent manner. The membrane association of rabphilin-3A was modestly enhanced in Rab3B-expressing PC12 cells relative to Rab3A-overexpressing cells. In addition, overexpression of Rab3A modestly inhibited Ca2+-evoked NE release, whereas Rab3B and a GTP binding mutant (Rab3B N135I) markedly stimulated the efficiency of [3H]NE secretion by PC12 cells (i.e. secretion normalized to total cell radioactivity). Expression of Rab3B and Rab3B N135I increased not only the efficiency of NE secretion but also the accumulation of [3H]NE into LDCVs (i.e. the secretory cargo available for secretion). Neither of these effects was attributable to changes in the numbers of LDCVs nor the docking of LDCVs at the plasma membrane. Our results indicate that Rab3A and Rab3B have similar membrane targeting properties and are capable of interacting with the same putative downstream effector; i.e. rabphilin-3A. However, these isoforms are functionally distinct monomeric GTPases with Rab3B stimulating a late step in Ca2+-evoked secretion when expressed in PC12 cells.

Animals↗

PubMed1996

Differential sensitivity of mice bred for stress-induced analgesia to morphine and ACEA-1011 in the formalin test.

The antinociceptive effect of morphine, an opioid receptor agonist, and ACEA-1011, a novel NMDA receptor/glycine site antagonist, was examined in the formalin test in mice selectively bred for high (HA) and low (LA) swim stress-induced analgesia (SSIA). A subcutaneous (SC) injection of formalin produced a biphasic nociceptive response in both lines. HA mice spent more time licking the injected paw than the LA mice in both phases of the formalin test. Morphine was equally potent in the early phase in both lines, but it was more potent in HA mice than in LA mice in the tonic late phase of the formalin test. Similarly, ACEA-1011 produced an equally potent antinociceptive effect in the early phase in both lines; however, the compound was more potent in LA mice than in HA mice in the tonic late phase of the formalin test. These data suggest that in HA mice antinociception in the tonic late phase of the formalin test is mediated largely by an opioid-mediated mechanism, whereas in the opioid-deficient LA line at least a nonopioid-mediated mechanism involving the NMDA receptor is also implicated.

Analgesia↗

PubMed1996

Subtype-selective inhibition of N-methyl-D-aspartate receptors by haloperidol.

Previous studies indicate that haloperidol, a therapeutically useful antipsychotic drug, inhibits neuronal N-methyl-D-aspartate (NMDA) responses and has neuroprotective effects against NMDA-induced brain injury. To further characterize this inhibition, we used electrical recordings to assay the effects of haloperidol on four diheteromeric subunit combinations of cloned rat NMDA receptors expressed in Xenopus laevis oocytes: NR1A coexpressed with NR2A, NR2B, NR2C, or NR2D. Haloperidol selectively blocks NR1A/2B subunit combinations (IC50 = approximately 3 microM; maximum inhibition, approximately 85%), whereas the other subunit combinations are > or = 100-fold less sensitive (IC50 = >300 microM). Inhibition of NR1A/2B receptors is insurmountable with respect to glutamate and glycine and does not exhibit voltage dependence. The splice variant combinations NR1B/2B and NR1e/2B are also blocked by haloperidol. In oocytes from some frogs, 30-100 microM haloperidol induces potentiation of NR1A/2A receptor responses. NMDA responses in E16-17 rat cortical neurons cultured for < or = 10 days are inhibited by haloperidol at the same potency and to the extent as NR1/2B receptors (IC50 = approximately 2 microM; maximum inhibition, approximately 80%). In contrast, cells cultured for longer periods show a wide range of sensitivity. This change in pharmacology coincides with a developmental switch in subunit expression; from NR1 expressed with NR2B to NR1 coexpressed with NR2A and NR2B. Inhibition of macroscopic neuronal NMDA responses is mechanistically similar to inhibition of NR1A/2B receptors. Single-channel recordings from neurons show that antagonism is associated with a decrease in the frequency of channel openings and a shortening of mean channel open time. Collectively, our experiments indicate that haloperidol selectively inhibits NMDA receptors comprised of NR1 and NR2B subunits. Inhibition is consistent with action at a noncompetitive allosteric site that is distinct from the glutamate-, glycine-, and phencyclidine-binding sites and is probably mechanistically related to the atypical antagonist ifenprodil. Our results suggest that haloperidol can be used as a tool for investigating NMDA receptor subunit composition and can serve as a structural lead for designing novel subtype-selective NMDA receptor ligands.

Animals↗

PubMed1995

Infarct volume varies with rat strain and vendor in focal cerebral ischemia induced by transcranial middle cerebral artery occlusion.

We recently reported that the outcome of focal cerebral ischemia induced by intraluminal middle cerebral artery occlusion may differ depending upon a rat's strain and/or vendor. Sprague-Dawley rats originating from Taconic Laboratories and Charles River Laboratories had infarct volumes several fold larger than Sprague-Dawley rats originating from Simonsen Laboratories. The present study sought to determine whether these differences were restricted to an intraluminal technique or whether strain and vendor dependent differences will also exist in rats subjected to a transcranial method of focal cerebral ischemia. Accordingly, we permanently coagulated the middle cerebral artery via a transcranial approach in Sprague-Dawley rats originating from Simonsen Laboratories and Taconic Laboratories and in Simonsen Laboratories Fischer-344 rats. The cortical infarct volume significantly differed in the following order: Simonsen Laboratories Sprague-Dawley rats < Simonsen Laboratories Fischer-344 rats < Taconic Laboratories Sprague-Dawley rats. The subcortical infarct volume differed statistically in the following order: Simonsen Laboratories Sprague-Dawley rats < Taconic Laboratories Sprague-Dawley rats < Simonsen Laboratories Fischer-344 rats. These results along with our previous findings demonstrate that strain and vendor differences in the outcome of focal cerebral ischemia are independent of the technique applied.

Animals↗

PubMed1995

Intercellular adhesion molecule-1 gene expression by glial cells. Differential mechanisms of inhibition by IL-10 and IL-6.

The central nervous system contains two major glial cell types, astrocytes and microglia, which function as immune effector cells within the central nervous system. We have been studying the ability of glial cells to express gene products involved in immune responsiveness, with an emphasis on expression of ICAM-1. We demonstrated previously that three proinflammatory cytokines, TNF-alpha, IL-1 beta, and IFN-gamma, as well as IFN-gamma plus LPS, can enhance ICAM-1 expression by primary rat astrocytes. In this study, we examined ICAM-1 expression by primary rat microglia and found that only IFN-gamma and IFN-gamma/LPS enhance ICAM-1 gene expression. These data indicate that ICAM-1 expression by astrocytes and microglia is enhanced differentially by various proinflammatory cytokines. We next examined the effect of two cytokines, IL-10 and IL-6, on ICAM-1 expression. IL-10 alone has no effect on ICAM-1 expression, but it inhibits the enhancement of ICAM-1 intracellular and membrane protein expression in both cell types, although it has no influence on ICAM-1 steady-state mRNA levels. These results suggest that IL-10 affects ICAM-1 expression at the translational and/or post-translational level. IL-6 alone also had no effect on ICAM-1 expression in either astrocytes or microglia, but it inhibited induction of both ICAM-1 mRNA and protein expression in these cells. Inhibition of ICAM-1 mRNA steady-state levels by IL-6 was not the result of degradation of the ICAM-1 message, suggesting an effect at the transcriptional level. Thus, both IL-10 and IL-6 can inhibit ICAM-1 expression by glial cells, although they do so by contrasting mechanisms.

Animals↗

PubMed1995

Distribution and activity of calcineurin in rat tissues. Evidence for post-transcriptional regulation of testis-specific calcineurin B.

Calcineurin (CN), a Ca2+/calmodulin-regulated phosphatase 2B, plays an important role in many biological processes including T-cell signal transduction. In the present study, the distribution and activity of CN were investigated in rat tissues. CN has a wide tissue distribution, as measured by enzyme-linked immunosorbent assay. CN concentrations are 0.2-0.6 micrograms/mg protein in most tissues, while the brain contains 3-10-fold higher concentrations. Immunohistochemical analyses using a monoclonal antibody to CN B subunit reveals that CN is not evenly distributed but concentrated in specific cells, especially in the brain, kidneys and testis. The specific enzymic activity of CN in tissues is around 10 pmol.min.mg protein-1, except in brain and liver (60 pmol.min-1.mg protein-1 compared to 3.6 pmol.min-1.mg protein-1). The immunosuppressants cyclosporin A and tacrolimus, but not rapamycin, inhibit the phosphatase activity of CN derived from most tissues tested, while CN activity from liver was resistant to cyclosporin A. Furthermore, transcripts and protein of the common CN B subunit and of the testis-specific form of CN B subunit were analyzed. The common CN B subunit transcripts and protein are detected in all tissues. Transcripts for the 'testis-specific' CN B subunit are also found in brain, lung, thymus and heart, while the protein is only detected in testis. This indicates that the testis-specific CN B subunit gene expression is regulated at both transcriptional and posttranscriptional levels. The findings demonstrate that CN is a widely distributed protein phosphatase and that its activity is regulated in a tissue-specific manner.

Amino Acid Sequence↗

PubMed1995

The role of strain/vendor differences on the outcome of focal ischemia induced by intraluminal middle cerebral artery occlusion in the rat.

This study investigated the role of strain and vendor differences on the outcome of focal cerebral ischemia in the rat induced by occlusion of the middle cerebral artery by an intraluminal thread. The cortical infarct volumes (Mean +/- S.E.M.) were: 14.2 +/- 6.2 mm3 in Simonsen Laboratories Sprague-Dawley rats; 84.0 +/- 22.9 mm3 in Simonsen Laboratories Wistar rats; 223.3 +/- 23.6 mm3 in Taconic Laboratories Sprague-Dawley rats; and 239.5 +/- 30.7 mm3 in Charles River Laboratories Sprague-Dawley rats. Middle cerebral artery occlusion combined with bilateral common carotid artery occlusion for 60 min increased cortical infarct volumes to: 113.0 +/- 18.8 mm3; 152.4 +/- 21.1 mm3; 227.8 +/- 19.3 mm3; and 248.4 +/- 24.0 mm3, respectively. To control the effect of blood pressure as a variable contributing to the outcome of ischemia, additional experiments where performed in which the blood pressure in Simonsen Laboratories Sprague-Dawley rats was lowered to the level of the blood pressure in Taconic Laboratories Sprague-Dawley rats. Although this manipulation increased the cortical infarct volumes in Simonsen Laboratories Sprague-Dawley rats, the volumes were still less than those in Taconic Laboratories Sprague-Dawley rats. The results of the present study indicate that the outcome of ischemia in the intraluminal thread model may dramatically differ depending on the strain and vendor of animal used.

Animals↗

PubMed1995

Cloning and expression of a receptor for an insecticidal toxin of Bacillus thuringiensis.

Environmentally friendly toxins of Bacillus thuringiensis are effective in controlling agriculturally and biomedically harmful insects. However, little is known about the insect receptor molecules that bind these toxins and the mechanism of insecticidal activity. We report here for the first time the cloning and expression of a cDNA that encodes a receptor (BT-R1) of the tobacco hornworm Manduca sexta for an insecticidal toxin of B. thuringiensis. The receptor is a 210-kDa membrane glycoprotein that specifically binds the cryIA(b) toxin of B. thuringiensis subsp. berliner and leads to death of the hornworm. BT-R1 shares sequence similarity with the cadherin superfamily of proteins.

Amino Acid Sequence↗

PubMed1995

Blockade of morphine tolerance by ACEA-1328, a novel NMDA receptor/glycine site antagonist.

Recent studies indicate that competitive and non-competitive NMDA receptor antagonists can block the development of morphine tolerance. Since glycine is considered to be a co-agonist for activation of NMDA receptors we examined the effect of a novel bioavailable NMDA receptor/glycine site antagonist, 5-nitro-6,7-dimethyl-1,4-dihydro-2,3-quinoxalinedione (ACEA-1328), on the development of morphine tolerance. Administration of ACEA-1328 (20 mg/kg) completely blocked tolerance to morphine-induced antinociception in the tail flick test in CD-1 mice, without affecting the basal nociceptive response or potentiating morphine-induced antinociceptive effects. These data suggest that inhibition of NMDA receptor activity via blockade of the glycine co-agonist site is potentially viable as a therapeutic approach for preventing development of morphine tolerance.

Analgesics↗