Liminal gastrin does not activate rat stomach histidine decarboxylase

Summary Fasted rats have a low gastric histidine decarboxylase activity. I.v. infusion of heptadecapeptide gastrin for 2 h raised the enzyme activity. Intragastric perfusion with the same dose of gastrin and for the same period of time did not reproduce the effect of circulating gastrin. It is concluded that luminal gastrin, in contrast to circulating gastrin, does not activate rat stomach histidine decarboxylase.This study was supported by the Swedish Medical Research Council (04X-1007, 14X-4144) and by the Albert Påhlsson Foundation.     

Synthesis of sulfated glycosaminoglycans by the three cell types of the rabbit cornea in culture

Summary Rabbit corneal cells were cultivated for 21 days and then exposed to Na₂ ³⁵SO₄, a precursor of sulfated glycosaminoglycans (GAG). All 3 cell types of the cornea, the fibroblasts, the epithelial as well as the endothelial cells, synthesize GAG. The fractionation-patterns of the epithelial and endothelial GAG are almost identical and differ clearly from the one of fibrolastic GAG.Supported by SNSF, grant No. 3.534.71.     

Sulfatase activities towards the regulation of cell metabolism and signaling in mammals

In higher vertebrates, sulfatases belong to a conserved family of enzymes that are involved in the regulation of cell metabolism and in developmental cell signaling. They cleave the sulfate from sulfate esters contained in hormones, proteins, and complex macromolecules. A highly conserved cysteine in their active site is post-translationally converted into formylglycine by the formylglycine-generating enzyme encoded by SUMF1 (sulfatase modifying factor 1). This post-translational modification activates all sulfatases. Sulfatases are extensively glycosylated proteins and some of them follow trafficking pathways through cells, being secreted and taken up by distant cells. Many proteoglycans, glycoproteins, and glycolipids contain sulfated carbohydrates, which are sulfatase substrates. Indeed, sulfatases operate as decoding factors for a large amount of biological information contained in the structures of the sulfated sugar chains that are covalently linked to proteins and lipids. Modifications to these sulfate groups have pivotal roles in modulating specific signaling pathways and cell metabolism in mammals.     

Polyclinal,a new sulfated polyhydroxy benzaldehyde from the marine ascidianPolyclinum planum

Summary A new sulfated polyhydroxy benzaldehyde has been isolated from extracts of the temperate colonial ascidianPolyclinum planum. The structure of the new metabolite was solved by an X-ray crystallographic study. The highest concentration of this metabolite was found in the zooid-rich outer layers of this ascidian suggesting that it may represent a potential chemical defense against predators.     

Gastrin stimulated H+ secretion in amphibian gastric mucosa: Effect of tetrodotoxin

Summary The role of neural mechanisms in gastrin stimulated H⁺ secretion was studied using amphibian gastric fundic mucosa. Spontaneously secreting mucosae were converted to resting state (zero H⁺ secretory rate) using Burimamide. Following removal of burimamide, 3×10^–6 M tetrodotoxin did not block gastrin stimulation of H⁺ secretion indicating that neural mechanisms are not required.This work was supported by U.S. Public Health Service NIH Grant AM17315 and by the Medical Research Service of the Veterans Administration.     

On the location of the tetrapyrrole macrocycle of chlorophyll a in phospholipid vesicles and in hexadecane

Summary The state of chlorophyll a in phosphatidylcholine vesicles was examined. The results indicate that the chlorophylls are present in monomeric form. A kinetic study of chlorophyll reactions with K₂S₂O₈ and piperidine showed that these substances react with the porphyrin rings of pigments located on both vesicle faces, most probably within the polar headgroup region.Acknowledgments. This work was supported by the Research Committee and the Biophysics Research Group, University of Québec at Trois-Rivières.     

Postnatal undernutrition: effect on antral gastrin levels at a later age

Summary In rats undernutrition from birth to 14 days of age resulted in retardation of growth and diminution of antral gastrin concentration. When the 14-day-old undernourished rats were nutritionally rehabilitated, they grew at a faster rate, and at 27 days of age their body weight and the weight of various tissues of the gastrointestinal tract including the antrum reached the levels of the well-nourished littermate controls. In spite of this, antral gastrin concentration was found to be about one-half of that of the well-nourished littermates.Acknowledgments. I am indebted to Professor J. F. Rehfeld of Rigshospitalet, Copenhagen, for his generous supply of gastrin antisera. I whish to thank Mr S. Frandsen for his skilful technical assistance. The work was supported by grants from the Danish Medical Research Council, NOVO Research Fund and Christian den Tiendes Fond, Denmark.     

Hormone and forskolin-stimulated cyclic AMP accumulation in human lymphocytes: reliability of longitudinal time measurements

Summary Reliability of measurement of lymphocyte cyclic AMP synthesis in intact cells was estimated by taking 3 successive blood samples during a one-month period from 11 healthy volunteers. Isoproterenol and prostaglandin E₁-stimulated cyclic AMP accumulation were used to evaluate the activity of these two receptor activities in human lymphocytes. Forskolin-stimulated cyclic AMP accumulation was used to evaluate the activity of the Ns/catalytic subunit. Only for forskolin was significant reliability observed. For isoproterenol and prostaglandin E₁ significant reliability was observed only for male subjects.Acknowledgment. This work was supported in part by the following organizations: Chief Scientist's Office, Israel Ministry of Health; Herman Goldman Foundation, New York; United Jewish Endowment Fund of Greater Washington-Pollinger Foundation.     

Morphogenetic effect of precocene I and II onSchistocerca gregaria (Forsk)

Summary 4th instar nymphs ofSchistocerca gregaria exposed to precocene I and II by topical application metamorphosed precociously. The ED₅₀ of both compounds were evaluated and, unexpectedly, precocene I was found to be more active than precocene II. All adultiforms were identical and in an advanced form.Acknowledgments. This work was supported by grants from the Natural Sciences and Engineering Research Council of Canada and the Ministère de l'Education du Québec. We are grateful to Gaston Grégoire for rearing the insects.     

Neural discharge can be modulated by carotid arterial injection of gastrin-17 in rat hypothalamic paraventricular nucleus

Neural discharge in the hypothalamic paraventricular nucleus (PVN) was examined after gastrin-17 injection into the carotid artery in anesthetized rats. Neural discharge was increased by gastrin-17 injection into the carotid artery close to the cranium, and the response due to the gastrin was dose-dependent. No discharge response was seen when gastrin was injected into the jugular vein. These results suggest that gastrin circulating in the arterial blood can penetrate the blood brain barrier, and modulate neural PVN activity which is responsible for gastric acid secretion.     

Effects of hypo and hyperosmotic media on rabbit renal cortical slices

Summary Rabbit kidney cortex slices behave as osmometers when withstanding either hyperosmotic shocks or hypoosmotic shocks of amplitude up to P₁/P₂=1.25. For hypo-osmotic shocks of amplitude larger or equal to P₁/P₂=1.5 a volume regulation process occurs. Na⁺ is the main osmotic effector implicated in volume control.This work has been aided by a grant 1.5.422.82F from the FNRS to R.G. We wish to thank Mr J.M. Theate for his skilful assistance.     

The structures of minor congeners of detoxin complex,the selective antagonist of blasticidin S1

Summary The structures of the minor congeners of detoxin complex, viz., detoxins E₁, C₁, C₂, C₃, B₁, B₃ and A₁ have been established on the basis of spectral and degradative evidence.Acknowledgment. This work was supported by a Grant-in-Aid for Special Project Research (510208) from the Ministry of Education, Science and Culture, Japan. We are grateful to Kaken Chemical Co. Ltd for the supply of the detoxin complex. This is Part V of studies of Detoxin Complex, the Selective Antagonists of Blasticidin S'. For Part IV, see Ogita et al.⁸.     

GABA-A-mediated gastrin release induced by baclofen in the isolated vascularly perfused rat stomach

Summary In order to investigate the role of peripheral GABA-B receptors, the effects of the putative GABA-B agonist baclofen on immunoreactive gastrin release from an isolated vascularly perfused rat stomach preparation were examined. The vascular infusion of baclofen at graded concentrations induced a dose-dependent increase in gastrin release; this was unaffected by the GABA-B antagonist delta-aminovaleric acid, but was fully prevented by the selective GABA-A antagonist bicuculline as well as by atropine or tetrodotoxin. These results suggest that the stimulant effects of baclofen are mediated by nervous cholinergic structures, associated with GABA-A receptors, and indicate that this GABA-B agonist must be regarded as a partial agonist of peripheral GABA-A receptors.     

GABA-A-mediated gastrin release induced by baclofen in the isolated vascularly perfused rat stomach

In order to investigate the role of peripheral GABA-B receptors, the effects of the putative GABA-B agonist baclofen on immunoreactive gastrin release from an isolated vascularly perfused rat stomach preparation were examined. The vascular infusion of baclofen at graded concentrations induced a dose-dependent increase in gastrin release; this was unaffected by the GABA-B antagonist delta-aminovaleric acid, but was fully prevented by the selective GABA-A antagonist bicuculline as well as by atropine or tetrodotoxin. These results suggest that the stimulant effects of baclofen are mediated by nervous cholinergic structures associated with GABA-A receptors, and indicate that this GABA-B agonist must be regarded as a partial agonist of peripheral GABA-A receptors.     

Isolation and fusion studies on protoplasts from pollen tetrads

Summary different enzymes were tested for isolation of intact protoplasts from pollen tetrads. About 80% isolation was achieved from pollen tetrads of Cajanus cajan and Zea mays and about 60% from Luffa cylindrica and Lycopersicon esculentum after 4 h of treatment with 5% cellulase. When these mononucleate protoplasts were incubated in presence of 0.05 M CaCl₂ in 0.3 M glucose at pH 10.5, 70–80% fusion was achieved. Fusion was rare in sodium nitrate solutions.This work was supported by a grant from the Indian Council of Agricultural Research, New Delhi (No. 1-32/73, Ed. I) in the form of a Senior Fellowship awarded to P. C. D.Work carried out at Molecular Cytogenetics Research Unit, Dept. of Genetics and Plant Breeding, Banaras Hindu University, Varanasi, India.     

The effect of pH and methylation on the interaction of deoxycholate with rat liver alcohol dehydrogenase

Summary The activation of rat liver alcohol dehydrogenase by deoxycholate depends on the anionic form of the steroid. Methylation of the enzyme protein leads to an increase of both turnover number and K_m for ethanol and to a change in the effect of deoxycholate, which behaves as an inhibitor. It is suggested that the steroid and methylation effects depend on the same basic mechanism, in which one or more Lys groups are involved.Acknowledgment. We thank Professor A. Guerritore for his help and advice. This work was supported by a grant from the Italian Consiglio Nazionale delle Ricerche.     

Aging and endothelin-1 induced vascular contractions

Summary Contractions produced by endothelin-1 (0.3–30 nM) have been investigated in aorta, renal arteries and mesenteric arteries from 2- and 24-month-old Sprague-Dawley rats. In senescent rats the EC₅₀ values of endothelin-1 for aorta and renal artery were significantly increased (aorta: from 6.2 to 12 nM; renal artery: from 5.2 to 7.8 nM). For mesenteric artery the EC₅₀ value (4.3 nM) was unchanged by aging, whereas the maximal contractile response to endothelin-1 was enhanced (from 8.3 to 11.7 mN). In contrast, there was no significant age-related difference in the maximal endothelin-1 response of aorta and renal artery. The present data demonstrate a reduced sensitivity for aorta and renal artery and an enhanced maximal response to endothelin-1 in the mesenteric artery in senescent rats.     

Multimeric structures of HLA-G isoforms function through differential binding to LILRB receptors

The non-classical Human leukocyte antigen G (HLA-G) differs from classical HLA class I molecules by its low genetic diversity, a tissue-restricted expression, the existence of seven isoforms, and immuno-inhibitory functions. Most of the known functions of HLA-G concern the membrane-bound HLA-G1 and soluble HLA-G5 isoforms, which present the typical structure of classical HLA class I molecule: a heavy chain of three globular domains α₁–α₂–α₃ non-covalently bound to β-2-microglobulin (B2M) and a peptide. Very little is known of the structural features and functions of other HLA-G isoforms or structural conformations other than B2M-associated HLA-G1 and HLA-G5. In the present work, we studied the capability of all isoforms to form homomultimers, and investigated whether they could bind to, and function through, the known HLA-G receptors LILRB1 and LILRB2. We report that all HLA-G isoforms may form homodimers, demonstrating for the first time the existence of HLA-G4 dimers. We also report that the HLA-G α₁–α₃ structure, which constitutes the extracellular part of HLA-G2 and HLA-G6, binds the LILRB2 receptor but not LILRB1. This is the first report of a receptor for a truncated HLA-G isoform. Following up on this finding, we show that the α₁–α₃-Fc structure coated on agarose beads is tolerogenic and capable of prolonging the survival of skin allografts in B6-mice and in a LILRB2-transgenic mouse model. This study is the first proof of concept that truncated HLA-G isoforms could be used as therapeutic agents.     

Cholecystokinin-like peptides in avian brain and gut

Summary Extracts of turkey brain and jejunum contain a factor closely resembling the COOH-terminal octapeptide of porcine cholecystokinin (CCK). Turkey antral extracts contain factors distinguishable in immunochemical and gel filtration properties from the mammalian forms of gastrin and CCK. *** DIRECT SUPPORT *** A2025089 00007Acknowledgments. Skilled technical assistance was given by Elaine Clarke, Carol Higgins and Gavin Laing. Pure natural human G17 and G34 were generously provided by Prof. R.A. Gregory and Dr H.J. Tracy; pure natural porcine CCK33 was a generous gift from Prof. Viktor Mutt; the Squibb Institute for Medical Research kindly provided supplies of synthetic CCK8, and synthetic caerulein was a gift from Farmitalia Ltd.