Search PubMed⌕ Search

Biomedical subjects

B Weiss

Publications and source records attributed to B Weiss.

At least 289 records · Page 16Linked to original sources
PubMed1983

Effect of bestatin analogues and other compounds on enkephalin hydrolysis by an aminopeptidase from the mesophiles pseudomonas sp ATCC 11299A and chromobacterium violaceum ATCC 12540.

In our studies on newly synthesized compounds for their potential analgesic effect, we decided for purposes of convenience and economy to investigate non-mammalian sources for the presence of enkephalin degrading enzymes. An aminopeptidase that catalyzes the hydrolysis of the tyrosylglycyl bond of leucine- and methionine enkephalin was purified from the mesophiles Pseudomonas sp ATCC 11299a (Ps) and Chromobacterium violaceum ATCC 12540 (Cv). Each preparation also hydrolyzed to varying extents neutral dipeptides, tripeptides, tetrapeptides and amino acid beta-naphthylamides. The Ps enzyme has a pH optimum of 6.8, Km of 80 microM and a Vmax of 6.7 nmoles/min/mg of protein. The Cv enzyme has a pH optimum of 6.8-7.2, Km of 111 microM and a Vmax of 42 nmoles/min/mg of protein. Both are sulfhydryl enzymes since they are activated by dithiothreitol (DTT) and inactivated by p-chloro- and p-hydroxymercuribenzoate. They are not glycoproteins since they pass unretained through a Con A-Sepharose column. The activity lost by dialysis against EDTA can be restored, wholly or in part, by Co+2, Mg+2, Mn+2 and Ni+2; ions exerting an inhibitory effect were A1+3, Cd+2, Cu+2, Hg+2 and Zn+2. From a range of organic compounds, the greatest inhibition was elicited by the microbial peptides amastatin and bestatin. Several dipeptide analogues of bestatin, synthesized from DL-threo-2-amino-3-hydroxy-3-phenylpropanoic acid (AHPP) as the N-terminal residue in order to define the stereospecific requirements of the alpha, beta-functional groups for maximal activity, were not as active as the parent compound.

Aminopeptidases↗
PubMed1982

Interaction of drugs with calmodulin. Biochemical, pharmacological and clinical implications.

Calmodulin is a widely distributed, highly active, calcium-binding protein that influences a number of important biological events. Accordingly, agents that inhibit the activity of calmodulin should have profound pharmacological effects. Within the past few years, a number of compounds have been identified that inhibit calmodulin. The most potent of these described so far include certain antipsychotic drugs, smooth muscle relaxants, alpha-adrenergic blocking agents and neuropeptides. Studies of the physicochemical and structural properties of a variety of calmodulin inhibitors have shown that there are ionic and hydrophobic interactions between the drug and calmodulin. From the limited studies conducted so far, we conclude that, for a compound to inhibit calmodulin, it should carry a positive charge at physiological pH, presumably to interact with negative charges on the highly acidic calmodulin, and have hydrophobic groups, presumably to interact with lipophilic regions on calmodulin. But these two factors are not the only ones that are involved in inhibiting calmodulin, for many highly charged and highly hydrophobic agents have relatively little effect on calmodulin activity. The structural relationships between these ionic and hydrophobic regions and other, as yet identified, factors are also important. Many of the biochemical actions of the phenothiazine antipsychotic agents can be explained by the common mechanism of their binding to, and inhibiting, calmodulin. The question of whether these biochemical actions can explain their pharmacological and clinical effects is still unclear. The fundamental role calmodulin plays in biology suggests that this calcium binding protein may provide a new site for the pharmacological manipulation of biological activity. The calmodulin inhibitors described thus far hardly scratch the surface of this fertile area of research.

Antipsychotic Agents↗
PubMed1982

Altered adult behavior of mice following postnatal treatment with haloperidol.

Haloperidol (1 and 2 mg/kg) was administered SC daily to BALB/c and Swiss/Webster mice from postnatal days 4 through 21. Non consistent statistically significant drug effects were detected on growth and reflex development. Spontaneous motor activity increased significantly in both sexes of the Swiss/Webster outbred strain, and in the Balb/c males. Performance of a fixed ratio schedule of reinforcement of both male and female haloperidol-exposed mice was not statistically different from control performance. Interpretation of such data must take into account the sensitivity of the testing devices, the effects of repeated testing of a single animal, and the suitability of traditional statistical methods in developmental pharmacology and toxicology.

Analysis of Variance↗
PubMed1982

Role of exonuclease III in the base excision repair of uracil-containing DNA.

Mutants of Escherichia coli K-12 deficient in both exonuclease III (the product of the xth gene) and deoxyuridine triphosphatase (the dut gene product) are inviable at high temperatures and undergo filamentation when grown at such temperatures. In dut mutants, the dUTP pool is known to be greatly enhanced, resulting in an increased substitution of uracil for thymine in DNA during replication. The subsequent removal of uracil from the DNA by uracil-DNA glycosylase produces apyrimidinic sites, at which exonuclease III is known to have an endonucleolytic activity. The lethality of dut xth mutants, therefore, indicates that exonuclease III is important for this base-excision pathway and suggests that unrepaired apyrimidinic sites are lethal. Two confirmatory findings were as follows. (i) dut xth mutants were viable if they also had a mutation in the uracil-DNA glycosylase (ung) gene; such mutants should not remove uracil from DNA and should not, therefore, generate apyrimidinic sites. (ii) In the majority of the temperature-resistant revertants isolated, viability had been restored by a mutation in the dCTP deaminase (dcd) gene; such mutations should decrease dUTP production and hence uracil misincorporation. The results indicate that, in dut mutants, exonuclease III is essential for the repair of uracil-containing DNA and of apyrimidinic sites.

DNA Repair↗
PubMed1982

Specific mutator effects of ung (uracil-DNA glycosylase) mutations in Escherichia coli.

Studies of trpA reversions revealed that G:C leads to A:T transitions were stimulated about 30-fold in E. coli ung mutants, whereas other base substitutions were not affected. A dUTPase (dut) mutation, which increases the incorporation of uracil into DNA in place of thymine, had no significant effect on the rate of G:C leads to A:T transitions. The results support the proposal that the glycosylase functions to reduce the mutation rate in wild-type cells by acting in the repair of DNA cytosine residues that have undergone spontaneous deamination to uracil. Further support was provided by the finding that when lambda bacteriophages were treated with bisulfite, an agent known to produce cytosine deamination, the frequency of clear-plaque mutants was increased an additional 20-fold by growth on an ung host. Bisulfite-induced mutations of the cellular chromosome, however, were about equal in ung+ and ung strains; it was found that during the treatment of ung+ cells with bisulfite, the glycosylase was inactivated.

Cytosine↗
PubMed1982

Interaction of beta-endorphin and other opioid peptides with calmodulin.

A highly purified preparation of calmodulin activated a calmodulin-deficient phosphodiesterase by more than 10-fold. This activation of phosphodiesterase by calmodulin was completely inhibited by two opioid peptides, beta-endorphin and dynorphin, at concentrations that had no appreciable effect on the basal phosphodiesterase activity. By contrast, similar concentrations of other structurally related peptides, including alpha-endorphin, (des-Tyr1)-gamma-endorphin, Leu-enkephalin, and Met-enkephalin, failed to block calmodulin's activation of phosphodiesterase. The inhibition by beta-endorphin of calmodulin's action was not reversed by calcium or by the opiate antagonist naloxone but was overcome by increasing the concentration of calmodulin. Equilibrium dialysis studies showed that 125I-labeled beta-endorphin bound directly to calmodulin in a saturable, calcium-dependent manner with a dissociation constant of approximately 4.6 microM. There was substantially less binding of beta-endorphin to troponin-C and little or no calcium-dependent binding of beta-endorphin to bovine serum albumin, lactalbumin, or histone. This interaction of beta-endorphin with calmodulin was similar in several respects to the interaction of certain antipsychotic drugs to calmodulin and may explain certain of the peptide's biochemical effects.

Animals↗
PubMed1981

Effect of sympathetic input on ontogeny of beta-adrenergic receptors in rat pineal gland.

The ontogeny of beta-adrenergic receptors was investigated in the pineal glands of rats 1-64 days of age. The density of beta-receptors increased about 3-fold between 1 and 16 days of age and decreased slightly by 64 days, correlating temporally with the development of the sensitivity of adenylate cyclase to norepinephrine in pineal gland. Preventing adrenergic innervation of the pineal gland by neonatal ganglionectomy or decentralization failed to prevent the development of beta-adrenergic receptors in pineal gland. Bilateral adrenal demedullation alone or in combination with ganglionectomy also failed to prevent the normal developmental increase of beta-receptors in the gland. These results, showing that the ontogeny of pineal beta-receptors correlated temporally with that of the responsiveness of adenylate cyclase to adrenergic neurohormones, support the hypothesis that the responsiveness of tissues ot beta-agonists is dependent on the development of the beta-receptor. In addition, these experiments show that the beta-adrenergic receptor can develop even in the absence of sympathetic innervation or circulating catecholamines produced by the adrenal medullae.

Adrenergic Fibers↗
PubMed1981

Electrical stimulation of sympathetic nerves increases the concentration of cyclic AMP in rat pineal gland.

Electrical stimulation of the superior cervical ganglia causes a rapid increase in the concentration of cyclic AMP in the pineal gland of rats. This effect is dependent upon the frequency, voltage, and duration of the stimulus and is markedly potentiated by pretreating the animals with desmethylimipramine. The increase in cyclic AMP is blocked by prior treatment of the rats with reserpine, bretylium, or propanolol but not with phentolamine. These results provide direct evidence that electrical stimulation of sympathetic nerves increases cyclic AMP in a target organ through the release of norepinephrine from presynaptic terminals acting on postsynaptic beta-adrenergic receptors.

Animals↗