Oxytocin-induced release of prostaglandin-like substance in isolated rat uterus

Isolated rat uterine horns were incubated in van Dyke-Hastings solution containing 1.0 mU/ml of oxytocin (Pitocin) at 30°C for 60 to 90 min. The uterine strips were found to remain strongly contracted throughout the incubation period and release into the bathing fluif a prostaglandin-like activity which was detectable by bioassays on the isolated rat uterine and stomach preparations. It was also found that ethyl acetate used in the extraction procedure had a potent inhibitory effect on the responses of the rat uterine and stomach strips to oxytocin and PGF_2α.     

Assay of prostaglandin-like substances in faeces and their measurement in ulcerative colitis

A method is described for extracting and measuring prostaglandin-like substances from faeces. Bioassay has shown virtual absence of activity in stools from normal people (8 subjects) but raised levels in stools from patients with active ulcerative colitis (16 observations on 6 patients). The relevance of these observations to the mode of action of sulphasalazine is discussed and suggestions for possible applications of this method to other problems made.     

The pharmacology of prostaglandin-like substances released from guinea-pig lungs during anaphylaxis

The pharmacology of the prostaglandins (PGs) and thromboxanes (Txs) released from immunologically challenged guinea-pig lungs is related to their roles in the anaphylactic response.6-oxo-PGF_1α probably contributes substantially to bronchoconstriction during anaphylaxis.TxB₂ may contribute to the anaphylactic response by increasing SRS-A release and by stimulating leucotaxis.The 15-oxo metabolites of PGE₂ and PGF_2α are rather weak spasmogens, but might modify respiratory muscle contractions and pulmonary vascular resistance.The 15-oxo 13,14 dihydro metabolites of PGE₂, PGF_2α and TxB₂ were inactive in the systems studied, suggesting an important inactivating role for the 13:14 reductase enzyme.     

Evidence against the release of prostaglandin-like material from isolated intestinal tissue by pure cholera toxin

Prostaglandin-like material was released from finely cut guinea-pig ileum or human intestinal mucosa during incubation with Krebs solution. The tissue inactivated some of the released material and added PGE₂. There was no significant change in release of prostaglandin-like material when pure cholera toxin was incubated with guinea-pig ileum or human intestinal mucosa. The work is discussed in relation to the action of cholera toxin $\text{in vivo}$.     

Evidence against the release of prostaglandin-like material from isolated intestinal tissue by pure cholera toxin.

Prostaglandin-like material was released from finely cut guinea-pig ileum or human intestinal mucosa during incubation with Krebs solution. The tissue inactivated some significant change in release of prostaglandin-like material when pure cholera toxin was incubated with guinea-pig ileum or human intestinal mucosa. The work is discussed in relation to the action of cholera toxin in vivo.     

Suppression of glial glutamine release to the extracellular fluid studied in vivo by NMR and microdialysis in hyperammonemic rat brain

Release of glial glutamine (GLN) to the extracellular fluid (ECF), mainly mediated by the bidirectional system N transporter SN1, was studied in vivo in hyperammonemic rat brain, using (15)N-nuclear magnetic resonance (NMR) to monitor intracellular [5-(15)N]GLN and microdialysis/gradient (1)H-(15)N heteronuclear single-quantum correlation NMR to analyse extracellular [5-(15)N]GLN. GLN(ECF) was elevated to 2.4 +/- 0.2 mm after 4.5 h of intravenous ammonium acetate infusion. The [GLN(i)]/[GLN(ECF)] ratio (i = intracellular) was 9.6 +/- 0.9, compared with 17-20 in normal brain. GLN(ECF) then decreased substantially at t = 4.9 +/- 0.1 h. Comparison of the time-courses of intra- and extra-cellular [5-(15)N]GLN strongly suggested that the observed decrease reflects partial suppression of glial GLN release to ECF. Suppression also followed elevation of GLN(ECF) to 1.9 mM, resulting in a [GLN](i)/[GLN(ECF)] ratio of 8.4, upon perfusion of alpha-(methylamino)isobutyrate which inhibits neuronal uptake of GLN(ECF) mediated by sodium-coupled amino acid transporter (SAT). The results provide first evidence for bidirectional operation of SN1 in vivo, and clarify the effect of transmembrane GLN gradient on glial GLN release at physiological Na(+) gradient. Implications of the results for SN1 as an additional regulatory site in the glutamine/glutamate cycle and utility of this approach for examining the role of GLN in an experimental model of fulminant hepatic failure are discussed.     

Prostaglandins and cholera: The occurrence of prostaglandin-like smooth muscle contracting substances in cholera diarrhoea

Prostaglandin-like smooth muscle contracting substances were identified in acid lipid extracts of diarrhoeal faeces taken from patients presenting clinical symptoms of cholera. Five out of the eleven cases studied were bacteriologically confirmed as cholera. The PG-like activity in the individual samples ranged from 3 – 27 ng PGE₂ equivalents /ml of diarrhoeal stool. Parallel bioassay and thin-layer chromatographic analysis of the extracts indicated that about 60% of the activity was due to an F-type PG, 15% to an E-type PG and the rest to unidentified lipid substance(s). It is proposed that increased PG production in cholera (indicated by these findings) may at least contribute to the disease.     

Suppression of peeling during the release of O-glycans by hydrazinolysis

The analysis of O-glycans is essential for better understanding their functions in biological processes. Although many techniques for O-glycan release have been developed, the hydrazinolysis release method is the best for producing O-glycans with free reducing termini in high yield. This release technique allows the glycans to be labeled with a fluorophore and analyzed by fluorescence detection. Under the hydrazinolysis release conditions, a side reaction is observed and causes the loss of monosaccharides from the reducing terminus of the glycans (known as peeling). Using bovine fetuin (because it contains the sialylated O-glycans most commonly found on biopharmaceuticals) and bovine submaxillary gland mucin (BSM), here we demonstrate that peeling can be greatly reduced when the sample is buffer exchanged prior to hydrazinolysis with solutions of either 0.1% trifluoroacetic acid (TFA) or low-molarity (100, 50, 20, and 5 mM) ethylenediaminetetraacetic acid (EDTA). The addition of calcium chloride to fetuin resulted in an increase in peeling, whereas subsequent washing with EDTA abolished this effect, suggesting a role of calcium and possibly other cations in causing peeling. The presented technique for sample preparation prior to hydrazinolysis greatly reduces the level of undesirable cleavage products in O-glycan analysis and increases the robustness of the method.     

突触前代谢型谷氨酸受体调节神经递质的释放

谷氨酸通过激活离子型受体（iGluR)介导快速兴奋性突触传递,参与脑内几乎所有生理过程。谷氨酸过量释放可导致与脑缺血,缺氧及变性疾病有关的兴奋毒作用,最终引起神经元的死亡。代谢型谷氨酸受体（mGluRs)是一个与G－蛋白偶联的受体家族,分三型共八个亚型。其中Ⅱ和Ⅲ型mGluRs主要位于突触前,发挥对谷氨酸释放的负反馈调节。Ⅲ型mGluRs中的mGluR7位于谷氨酸能末梢突触前膜的活性区,发挥自身受体的作用,对正常情况下突触传递过程的谷氨酸释放进行负反馈调节;而属于Ⅱ型的mGluR2及属于Ⅲ型的mGluR4和mGluR8,则位于远离突有膜活性区的外突触区,因而正常突触传递过程中释放的谷氨酸量不能激活它们。只有在突触传递增强的情况下才被激活,抑制递质的释放。国外,mGluRs还分布在GABA能纤维末梢,通过突触前机制抑制GABA的释放。对突触前膜受体尤其是位于外突触区的mGluRs受体的研究,将有可能开发出理想的工具药,从而预防和阻止谷氨酸过量释放引起的神经毒及神经元的死亡。     

Suppression of nigrostriatal and mesolimbic dopamine release in vivo following noradrenaline depletion by DSP-4: a microdialysis study.

Pretreatment of rats with the noradrenergic neurotoxin DSP-4 selectively reduced regional levels of noradrenaline in the brain by more than 75%, and decreased the concentration of endogenous DA in microdialysates of the caudate nucleus and nucleus accumbens by 52% and 28%, respectively. Results support the hypothesis that central noradrenergic mechanisms facilitate nigrostriatal and mesolimbic dopamine transmission in vivo.     

Suppression of tyrocidine production by purine nucleotides and related substances in Bacillus brevis

Bacillus brevis (ATCC 8185) produces an antibiotic peptide, tyrocidine. We found that adenosine or 5'-AMP suppressed the production of tyrocidine with half-maximum inhibition at 100-300 microM. This inhibition was specific to the production of tyrocidine since neither adenosine nor 5'-AMP showed any effect on bacterial growth. Cyclic nucleotides had no effect. These results suggest that adenosine, 5'-AMP or its metabolite was specifically involved in the regulation of tyrocidine production.     

Suppression of histone deacetylation in vivo and in vitro by sodium butyrate

In HeLa cells which have been exposed to 5 mM sodium butyrate for 21 h, the level of histone acetylation is greatly increased as compared to control cells (Riggs, M.G., Whittaker, R.G., Neumann, J.R., and Ingram, V.R. (1977) Nature 268, 462-464). Our experiments indicate that the increase in the relative amounts of multiacetylated forms of histones H4 and H3 following butyrate treatment is the result of an inhibition of histone deacetylase activity.     

Suppression of expulsion of Aspiculuris tetraptera in hydrocortisone and methotrexate treated mice.

Hydrocortisone treated male and female mice, given a primary infection with Aspiculuris tetraptera, did not reject the worms during the third week of infection. Mice given hydrocortisone during the first week of infection had elevated worm burdens on day 10, suggesting that some worm loss was encountered during the anterior migration in control mice. Furthermore, this temporary period of treatment was sufficient totally to suppress rejection and to allow the parasite to persist until day 28. Methotrexate also significantly delayed rejection, but larval growth was retarded in treated mice. These results, it is suggested, add strength to the hypothesis that the loss of A. tetraptera in a primary infection in mice, is an immunological phenomenon.     

Modification of rat liver RNA polymerase I after in vivo stimulation by hydrocortisone or methylisobutylxanthine

Following in vivo administration of hydrocortisone or methylisobutylxanthine to rats, higher levels (1.5- to 2.3-fold) of RNA polymerase I activity are present in liver nuclei and nucleoli of the treated animals as compared to control animals. The elevated specific activity is retained after purification of the enzyme under conditions where the enzyme is dependent on exogenous template for activity. The elevated polymerase activity in nuclei, nucleoli, and soluble enzyme can be destroyed by mild trypsin treatment which results in a rapid decay of the specific activity to the control level. Under these conditions, the control polymerase I activity is stable. The results indicate that in vivo stimulation by hydrocortisone or methylisobutylxanthine results in a conversion of the enzyme to a form that is catalytically more active but has an increased sensitivity to proteolysis.     

Suppression of superoxide release from human monocytes by somatostatin-related peptides.

Somatostatin and octreotide share with vasoactive intestinal peptide the property of having an inhibitory effect on leukocyte functions. While there are studies reporting the inhibitory effect of the latter on respiratory burst in human monocytes, no such reports are available about similar inhibitory effects of the former. The aim of the present study was to investigate such effects of somatostatin and octreotide on human monocytes. Release of superoxide anion from monocytes was measured by superoxide dismutase-inhibitable reduction of cytochrome c in vitro. Somatostatin 1-14, somatostatin 1-28 and octreotide inhibited release of superoxide anion from stimulated monocytes. Formylpeptide-stimulated reduction of cytochrome c was inhibited by 1 mumol/l of octreotide and somatostatin 1-14 by about 50% and 35%, respectively. The effect was dose-dependent with half-maximal effective peptide concentrations at about 10 nmol/l. Somatostatin 1-28, which is the major form found in circulating plasma, also antagonized formylpeptide-stimulated respiratory burst activity; when directly compared to the effect of 1 mumol/l of somatostatin 1-14, somatostatin 1-28 was significantly more active (P less than 0.05). Our observations suggest that somatostatin-related peptides have a regulatory role in oxygen radical metabolism and a mediator role in the neuro-immune axis.