ABSTRACT
To investigate the physiological roles of arginine vasotocin (AVT) and isotocin (IT) in osmoregulatory process in gilthead sea bream (Sparus aurata), a time course study (0, 12h, and 1, 3, 7 and 14 days) has been performed in specimens submitted to hypoosmotic (from 40 salinity to 5 salinity) or hyperosmotic (from 40 salinity to 55 salinity) challenges. Plasma and liver osmoregulatory and metabolic parameters, as well as AVT and IT pituitary contents were determined concomitantly with hypothalamic pro-vasotocin (pro-VT) and pro-isotocin (pro-IT) mRNA expression levels. Previously, sequences coding for pro-VT and pro-IT cDNAs were cloned. Two osmoregulatory periods related to plasma osmolality and metabolic parameter variations could be distinguished: i) an adaptative period, from 12h to 3 days after transfer, and ii) a chronic regulatory period, starting at day 3 after transfer. Higher values in hypothalamic pro-VT and pro-IT mRNA expression as well as in pituitary AVT and IT storage levels in both hypo- and/or hyper-osmotic transfers have been distinguished. These increase correlated with changes in plasma cortisol levels, suggesting an interaction between this hormone and pro-VT expression. Furthermore, pro-IT expression enhancement also suggests a role of the isotocinergic system as a modulator in the acute stress response induced by hyper-osmotic challenge in S. aurata.
Subject(s)
Osmoregulation/physiology , Oxytocin/analogs & derivatives , Sea Bream/physiology , Vasotocin/physiology , Amino Acid Sequence , Animals , Base Sequence , Hydrocortisone/blood , Hypothalamus/metabolism , Male , Molecular Sequence Data , Osmolar Concentration , Oxytocin/physiology , Pituitary Gland/metabolism , Protein Precursors/chemistry , Protein Precursors/metabolism , Salinity , Sequence AlignmentABSTRACT
An HPLC assay with solid-phase extraction and fluorescence derivatization was developed for measurement of arginine vasotocin (AVT) and isotocin (IT) in the neural tissues of fish. The efficiency and usefulness of the method have been verified in experiments by examination of peptides concentrations in brains of three fish species. The day-night changes in neuropeptides levels have been studied in brains of adult sea bream (Sparus aurata) and juvenile Atlantic salmon (Salmo salar). Seasonal fluctuations have been investigated in brains of three-spined sticklebacks (Gasterosteus aculeatus). The AVT and IT biosynthesis in brain seems to be controlled independently and probably each neuropeptide plays a different role in a circadian time-keeping system and an endocrine calendar in fish.
Subject(s)
Brain/metabolism , Chromatography, High Pressure Liquid/methods , Fishes/metabolism , Oxytocin/analogs & derivatives , Vasotocin/analysis , Animals , Brain Chemistry , Circadian Rhythm , Female , Male , Oxytocin/analysis , Oxytocin/metabolism , Seasons , Vasotocin/metabolismABSTRACT
Muramyl tripeptide phosphatidylethanolamine (MTP-PE), a synthetic lipophilic analogue of muramyl dipeptide, stimulates monocytes/macrophages to kill a variety of tumor cells in vitro and in vivo. Encapsulation of MTP-PE into multilamellar liposomes (L-MTP-PE) was specifically designed for in vivo targeting to macrophages by i.v. infusion and is the only form of the drug currently available for clinical trials (CGP 19835A Lipid). L-MTP-PE is presently undergoing clinical trials in patients with recurrent osteosarcoma and melanoma. L-MTP-PE combined with other anticancer agents may thus improve long-term cure rates of patients with this diseases.