Benzolactam growth hormone secretagogues: Replacement of the C-3 amide bond in L-692,429

The synthesis and structure-activity relationships of various C-3 amide bond modifications in the novel nonpeptidyl growth hormone secretagogue L-692,429 are described. Several C-3 amide surrogates were prepared and the urea moiety was found to exhibit growth hormone releasing activity similar to that observed with L-692,429.     

Comparison of the active and inactive chromatin structures of genes transcribed by RNA polymerases I and II

The coding sequences of the yeast 35S rDNA gene and of the yeast galactokinase gene both show clear staphylococcal nuclease nucleosome profiles under conditions in which the gene is inactive (galactokinase) or less active (rDNA). Under conditions of more active expression, the galactokinase gene shows marked smearing in the digestion profiles. The rDNA gene shows a qualitatively similar change in digestion patterns. There is a typical nucleosomal DNase I ladder on the coding sequences of both genes, regardless of the state of activity. In contrast to the coding sequences, the rDNA upstream region chromatin shows a nonnucleosomal profile. The nonnucleosomal character is more pronounced when the gene is more active. On the galactokinase upstream region chromatin, there is a nucleosomal structure, with some minor modifications, when the gene is inactive and a clear nonnucleosomal structure when the gene is expressed.     

Characterisation of substance P-induced endocytosis of NK1 receptors on enteric neurons

Immunoreactivity for NK1 receptors is confined to specific nerve cell bodies in the guinea-pig ileum, including inhibitory motor neurons and secretomotor neurons. In the present work, endocytosis of NK1 receptors in these enteric neurons was studied following addition of substance P (SP) to isolated ileum. NK1 receptors were localised with antibodies against the C-terminus of this receptor. Some preparations were incubated with SP tagged with the fluorescent label, Cy3.18, so that the fate of SP bound to receptors could be followed. Preparations were analysed by confocal microcopy. In tissue that was incubated at 4° C in the absence of SP, most NK1 receptor immunoreactivity (IR) was confined to surface membranes of nerve cells. At 37° C in the presence of 10⁻⁷ M SP (plus 3×10⁻⁷M tetrodotoxin to prevent indirect activation via other neurons) the neuronal NK1 receptor was rapidly internalised. After 5 min, NK1 receptor IR was partially internalised, at 20 min NK1 receptor IR was throughout the cytoplasm and in perinuclear aggregates and at 30 min it was again at the cell surface. SP-induced NK1 receptor endocytosis was inhibited by the specific NK1 receptor antagonist, SR140333. Cy3-SP was colocalised with NK1 receptor IR and was internalised with the NK1 receptor. These results show that enteric neurons exhibit authentic NK1 receptors that are rapidly internalised when exposed to their preferred ligand.     

Tuning posture to body load: decreases in load produce discrete sensory signals in the legs of freely standing cockroaches

Decreases in load are important cues in the control of posture and walking. We recorded activities of the tibial campaniform sensilla, receptors that monitor forces as strains in the exoskeleton, in the middle legs of freely moving cockroaches. Small magnets were attached to the thorax and body load was changed by applying currents to a coil below the substrate. Body position was monitored by video recording. The tibial sensilla are organized into proximal and distal subgroups that have different response properties and reflex effects: proximal sensilla excite extensor motoneurons while distal receptors inhibit extensor firing. Sudden load decreases elicited bursts from distal sensilla, while increased load excited proximal receptors. The onset of sensory discharges closely approximated the time of peak velocity of body movement in both load decreases and increases. Firing of distal sensilla rapidly adapted to sustained unloading, while proximal sensilla discharged tonically to load increases. Load decreases of small amplitude or at low rates produced only inhibition of proximal activity while decrements of larger size or rate elicited distal firing. These response properties may provide discrete signals that either modulate excitatory extensor drive during small load variations or inhibit support prior to compensatory stepping or initiation of swing.     

Ontogeny of the Digestive and Feeding Systems in the Anemonefish Amphiprion Melanopus

Ontogenetic growth and development in the anemonefish Amphiprion melanopus (Pomacentridae) is very rapid when compared to other tropical and temperate fish species. A. melanopus hatched with a highly differentiated digestive tract and the ability to capture and ingest prey items. Their alimentary tract changes rapidly throughout the larval period. Concurrent with yolksac absorption at three days after hatching was the development of the stomach followed by calcification of the jaw structures. This period of acute structural change may be a critical period in their development. Metamorphosis coincided with settlement at 8 days after hatching and was marked by calcification of fins and acquirement of adult coloration. The rapid development found in this species may be a specialisation to enhance the return of larvae to a patchy and highly specific settlement habitat.