Zur Wirkung von Oxytocin auf einen autorhythmischen glatten Gefässmuskel

Summary The influence of oxytocine on the spontaneously contractile portal vein of the rat has been investigated. This octapeptide decreases the active tension and abolished it completely at a concentration of 5×10^–7g/ml. The effect is not caused by an adrenergic mechanism but by a direct action on the smooth muscle cell.     

Biological properties of synthetic Ser4-Arg8-oxytocin (Ile3-Ser4-Arginine vasopressin): Role of the residue No. 4 in the hormone-pressor receptor interaction

Résumé Les propriétés pharmacologiques de la Ser⁴-Arg⁸-ocytocine (Ser⁴-vasotocine) synthétique ont été étudiées. La substitution en position 4 de la glutamine par la sérine diminue considérablement l'activité pressique de la vasotocine, ce qui montre l'importance de cette position dans les interactions entre les hormones neurohypophysaires et le récepteur vasopressique.

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The authors are indebted to Dr.Albert Jöhl (Ciba-Geigy Laboratories) for a sample of synthetic Ser⁴-Arg⁸-oxytocin. They thank Mrs.Christine Gaullier for ther skilled technical assistance.     

The natriuretic action of [4-Leucine]-arginine-vasotocin

Zusammenfassung [Leu⁴]-Arginin-vasotocin wirkt so wohl an Katzen (Chloralose-Narkose, Mannit-Diurese) als auch an wachen Ratten (mit 0.9%-iger NACl-Lösung belastet) und wachen nicht vorbehandelten Hunden natriuretisch und diuretisch.     

A frequency-dependent switch from inhibition to excitation in a hippocampal unitary circuit

The hippocampus, a brain structure essential for memory and cognition, is classically represented as a trisynaptic excitatory circuit. Recent findings challenge this view, particularly with regard to the mossy fibre input to CA3, the second synapse in the trisynaptic pathway. Thus, the powerful mossy fibre input to CA3 pyramidal cells might mediate both synaptic excitation and inhibition. Here we show, by recording from connected cell pairs in rat entorhinal-hippocampal slice cultures, that single action potentials in a dentate granule cell evoke a net inhibitory signal in a pyramidal cell. The hyperpolarization is due to disynaptic feedforward inhibition, which overwhelms monosynaptic excitation. Interestingly, this net inhibitory synaptic response changes to an excitatory signal when the frequency of presynaptic action potentials increases. The process responsible for this switch involves the facilitation of monosynaptic excitatory transmission coupled with rapid depression of inhibitory circuits. This ability to immediately switch the polarity of synaptic responses constitutes a novel synaptic mechanism, which might be crucial to the state-dependent processing of information in associative hippocampal networks.     

Strategies for the design of inhibitors of aldose reductase, an enzyme showing pronounced induced-fit adaptations

Aldose reductase is involved in the polyol pathway, catalyzing the reduction of glucose to sorbitol. However, due to pronounced binding site adaptations, the enzyme can operate on a broad palette of structurally diverse substrates ranging from small aliphatic and aromatic aldehydes up to steroid-type ligands. A comparative analysis of the presently accessible crystal structures of aldose reductase complexes reveals four binding-competent protein conformations. Additional relevant conformers are detected through molecular dynamics simulations. They indicate an equilibrium of several conformers which is shifted towards the binding-competent geometries upon ligand binding. Such a manifold system with several alternative binding site conformers requires some tailored concepts in virtual screening. We followed two strategies, both successfully suggesting new micromolar inhibitors. In a first attempt, we concentrated on one preferred conformer and performed a virtual screening, assuming that the binding pocket of aldose reductase adopts only this conformation. In a second approach, we followed a ligand superpositioning method. Ligands were extracted in their bound conformations from three different crystal structures, all accommodating the ligands with different active site conformations. After merging these ligands into one supermolecule, mutual alignments were computed, taking candidate ligands from a screening database. The latter strategy also retrieved several structurally new inhibitors of micromolar potency.     

Differential distribution of TASK-1, TASK-2 and TASK-3 immunoreactivities in the rat and human cerebellum

In this work, the distributions of some acid-sensitive two-pore-domain K⁺ channels (TASK-1, TASK-2 and TASK-3) were investigated in the rat and human cerebellum. Astrocytes situated in rat cerebellar tissue sections were positive for TASK-2 channels. Purkinje cells were strongly stained and granule cells and astrocytes were moderately positive for TASK-3. Astrocytes isolated from the hippocampus, cerebellum and cochlear nucleus expressed TASK channels in a primary tissue culture. Our results suggest that TASK channel expression may be significant in the endoplasmic reticulum of the astrocytes. The human cerebellum showed weak TASK-2 immunolabelling. The pia mater, astrocytes, Purkinje and granule cells demonstrated strong TASK-1 and TASK-3 positivities. The TASK-3 labelling was stronger in general, but it was particularly intense in the Purkinje cells and pia mater.Received 25 February 2004; received after revision 19 April 2004; accepted 28 April 2004     

The role of increasing temperature variability in European summer heatwaves

Instrumental observations and reconstructions of global and hemispheric temperature evolution reveal a pronounced warming during the past approximately 150 years. One expression of this warming is the observed increase in the occurrence of heatwaves. Conceptually this increase is understood as a shift of the statistical distribution towards warmer temperatures, while changes in the width of the distribution are often considered small. Here we show that this framework fails to explain the record-breaking central European summer temperatures in 2003, although it is consistent with observations from previous years. We find that an event like that of summer 2003 is statistically extremely unlikely, even when the observed warming is taken into account. We propose that a regime with an increased variability of temperatures (in addition to increases in mean temperature) may be able to account for summer 2003. To test this proposal, we simulate possible future European climate with a regional climate model in a scenario with increased atmospheric greenhouse-gas concentrations, and find that temperature variability increases by up to 100%, with maximum changes in central and eastern Europe.     

Increased seasonality in Middle East temperatures during the last interglacial period

The last interglacial period (about 125,000 years ago) is thought to have been at least as warm as the present climate. Owing to changes in the Earth's orbit around the Sun, it is thought that insolation in the Northern Hemisphere varied more strongly than today on seasonal timescales, which would have led to corresponding changes in the seasonal temperature cycle. Here we present seasonally resolved proxy records using corals from the northernmost Red Sea, which record climate during the last interglacial period, the late Holocene epoch and the present. We find an increased seasonality in the temperature recorded in the last interglacial coral. Today, climate in the northern Red Sea is sensitive to the North Atlantic Oscillation, a climate oscillation that strongly influences winter temperatures and precipitation in the North Atlantic region. From our coral records and simulations with a coupled atmosphere-ocean circulation model, we conclude that a tendency towards the high-index state of the North Atlantic Oscillation during the last interglacial period, which is consistent with European proxy records, contributed to the larger amplitude of the seasonal cycle in the Middle East.     

Licht- und elektronenmikroskopische Befunde an den Geschmacksknospen der Axolotlzunge

Summary The investigation of the taste buds in the tongue of the neotene Mexican axolotl (Siredon mexicanum) by light and electron microscopy demonstrates 4 different cell types: 1) R-cells, marginal cells of less differentiated character. 2) G-cells, granulated cells in basal position. 3) Cells of type A with fibrills, vesicular elements, and dark bodies, showing supporting and secretory function. 4) Cells of type B with an agranular endoplasmic reticulum in stripe like arrangement, supposed to be receptor cells.