A preferred conformation in the vasoactive intestinal peptide (VIP). Molecular architecture of gastrointestinal hormones

The ORD spectrum of the vasoactive intestinal peptide (VIP) in water indicates a preferred conformation with low helix content. Addition of organic solvents, especially of trifluoroethanol, results, even at low solvent concentration, in spectra with pronounced helical character. The readiness of shorter chains, with C-terminal sequences of VIP, to take up helical conformation under the effect of organic solvents parallels their biological activity. This suggests that an “active architecture” may be required for the interaction between hormone and receptor.     

Comparison of seasonal growth and polyamine content in shoots of orchard-grown standard and genetic dwarf apple tress

Seasonal variations in growth rate, and polyamine and arginine content were determined in shoots of standard and genetic dwarf apples ( Malus domestica Borkh.) in orchard conditions. Putrescine, spermidine, spermine and arginine exhibited the same seasonal variations. Polyamine titer and arginine content were correlated. Putrescine, spermidine, spermine and arginine levels increased during March and April, reaching the maximum at the end of April. From the onset of May, they decreased gradually until they reached a steady level at the end of July and beginning August. Then the level increased until September when growth stopped. Shoots of both standard and dwarf trees started to grow in April, elongated slowly during the summer and ceased growth in September. Polyamine and arginine content of the shoots of standard apple trees were higher compared to the shoots of genetic dwarfs, but the concentration of polyamine and arginine were not correlated with the growth rate.     

Synthesis and properties of the cyclopentapeptide desthiomalformin

Desthiomalformin, cyclo-d-alanyl-d-alanyl-l-valyl-d-leucyl-l-isoleucyl, was synthesized by conventional methods. Cyclization of the open chain intermediate through the azide produced the cyclopentapeptide in short reaction time and in high yield and was not accompanied by cyclodimerization. The extreme readiness of the pentapeptide azide to form a cyclic structure can be attributed to the presence of alternating d and l residues in the sequence, a feature that should result in reverse turns stabilized by intramolecular hydrogen bonds. Thus the open chain intermediate could have a preferred cyclic conformation.Desthiomalformin has high thermal stability; it can be sublimed in vacuo without decomposition. It lacks, however, the biological activity of its parent compound, malformin.     

The vasoactive intestinal peptide (VIP): VI. The 17-norleucine analog of the sequence 14–28

A pentadecapeptide amide with the C-terminal sequence (14–28) of the vasoactive intestinal peptide (VIP), but with the methionine residue in position 17 replaced by l-norleucine, was synthesized. The synthesis was carried out through stepwise chain lengthening, by the in situ technique. The norleucine-containing pentadecapeptide, l-arginyl-l-lysyl-l-glutaminyl-l-norleucyl-l-alanyl-l-valyl-l-lysyl-l-lysyl-l-tyrosyl- l-leucyl-l-asparaginyl-l-seryl-l-isoleucyl-l-leucyl-l-asparaginamide, was as active in relaxing different smooth-muscle preparations as the methionine-containing parent sequence.     

Release of dopamine and norepinephrine by hypoxia from PC-12 cells

We examined the effects of hypoxia on the release of dopamine(DA) and norepinephrine (NE) from rat pheochromocytoma 12 (PC-12) cellsand assessed the involvement ofCa²⁺ and protein kinases instimulus-secretion coupling. Catecholamine release was monitored bymicrovoltammetry using a carbon fiber electrode as well as by HPLCcoupled with electrochemical detection (ECD). Microvoltammetricanalysis showed that hypoxia-induced catecholamine secretion(PO₂ ofmedium ~40 mmHg) occurred within 1 min after the onset of thestimulus and reached a plateau between 10 and 15 min. HPLC-ECD analysisrevealed that, at any level of PO₂, therelease of NE was greater than the release of DA. In contrast, inresponse to K⁺ (80 mM), DA releasewas ~11-fold greater than NE release. The magnitude ofhypoxia-induced NE and DA releases depended on the passage, source, andculture conditions of the PC-12 cells. Omission of extracellularCa²⁺ or addition of voltage-gatedCa²⁺ channel blockers attenuatedhypoxia-induced release of both DA and NE to a similarextent. Protein kinase inhibitors, staurosporine (200 nM) andbisindolylmaleimide I (2 µM), on the other hand, attenuatedhypoxia-induced NE release more than DA release. However, proteinkinase inhibitors had no significant effect onK⁺-induced NE and DA releases.These results demonstrate that hypoxia releases catecholamines fromPC-12 cells and that, for a given change inPO₂, NErelease is greater than DA release. It is suggested that proteinkinases are involved in the enhanced release of NE during hypoxia.

     

Cytokines and bacterial infections

During the recent 10–15 years a growing amount of knowledge has been accumulated on the role of cytokines in the pathogenesis and resistance to infections caused by nonviral agents, including a wide range of bacteria. Cytokines can be major mediators of the pathogenic effect in some diseases, and represent important defense mechanisms in others. Detailed knowledge on the role of the growing number of recognised cytokines is important, because it may represent means to combat and to prevent diseases caused by such infections.