The hemoglobin ␣-chain fragment PVNFKFLSH, which we have named hemopressin, produced dose-dependent hypotension in anesthetized rats, starting at 0.001 g/kg. The hypotensive effect of the peptide was potentiated by enalapril only at the lowest peptide dose. These results suggest a role for hemopressin as a vasoactive substance in vivo. The identification of these putative intracellular substrates for ep24.15 and ep24.16 is an important step toward the elucidation of the role of these enzymes within cells. Endopeptidase EC 3.4.24.15 (ep24.15; also referred to as thimet oligopeptidase) and endopeptidase EC 3. 4.24.16 (ep24.16; also referred to as neurolysin) were initially detected in and purified from rat brain homogenates (1, 2). The cloned rat brain ep24.16 (3) showed 80% similarity and 63% identity with the previously cloned rat testis ep24.15 (4). Both peptidases share most of their natural substrates, including bradykinin, neurotensin, opioids, angiotensin I, and gonadotrophinreleasing hormone (5, 6

The pineal hormone melatonin (5-methoxy-N-acetyl-tryptamine) has been reported to participate in important physiological processes. Although some of its biological actions seem to depend on a protein receptor at the membrane surface, melatonin is known to interact with a large variety of tissues and cells, suggesting that the molecule may not necessarily interact through a specific membrane receptor at a specific cell. Most discussions of melatonin activity have assumed that the molecule is highly hydrophobic. Contrary to belief, the present work shows that melatonin is soluble in a purely aqueous medium up to 5 x 10(-3) M and describes a new method of melatonin preparation which shows the high hydrophilicity of the molecule. The results presented will affect the current biological hypothesis on the need of a melatonin carrier in the blood stream or the mechanisms which allow the hormone to cross the cell membrane and interact at the level of the nucleus.

Cancer cachexia induces loss of fat mass that accounts for a large part of the dramatic weight loss observed both in humans and in animal models; however, the literature does not provide consistent information regarding the set point of weight loss and how the different visceral adipose tissue depots contribute to this symptom. To evaluate that, 8-week-old male Wistar rats were subcutaneously inoculated with 1 ml (2!10 7 ) of tumour cells (Walker 256). Samples of different visceral white adipose tissue (WAT) depots were collected at days 0, 4, 7 and 14 and stored at K80 8C (seven to ten animals/each day per group). Mesenteric and retroperitoneal depot mass was decreased to the greatest extent on day 14 compared with day 0. Gene and protein expression of PPARg2 (PPARG) fell significantly following tumour implantation in all three adipose tissue depots while C/EBPa (CEBPA) and SREBP-1c (SREBF1) expression decreased over time only in epididymal and retroperitoneal depots. Decreased adipogenic gene expression and morphological disruption of visceral WAT are further supported by the dramatic reduction in mRNA and protein levels of perilipin. Classical markers of inflammation and macrophage infiltration (f4/80, CD68 and MIF-1a) in WAT were significantly increased in the later stage of cachexia (although showing a incremental pattern along the course of cachexia) and presented a depot-specific regulation. These results indicate that impairment in the lipid-storing function of adipose tissue occurs at different times and that the mesenteric adipose tissue is more resistant to the 'fat-reducing effect' than the other visceral depots during cancer cachexia progression.

ESR spectra of spin labels placed at the membrane surface and at different depths of the bilayer core, and melatonin fluorescence in the presence of lipid vesicles, suggest an average shallow position for the hormone in the membrane. However, according to the melatonin ability to cross lipid bilayers, nitroxides placed deep in the bilayer were able to quench the melatonin fluorescence. Melatonin membrane partition coefficients were calculated for bilayers in different packing states, and similar and rather high values were found. The data presented here may be quite important to the understanding of melatonin physiological actions at the membrane level.

No abstract