pituitrin and phenylalanyl-leucyl-phenylalanyl-glutaminyl-prolyl-glutaminyl-arginyl-phenylalaninamide

Hypothalamic paraventricular and supraoptic nuclei are involved in the body fluid homeostasis. Especially vasopressin peptide and mRNA levels are regulated by hypo- and hyperosmolar stimuli. Other neuropeptides such as dynorphin, galanin and neuropeptide FF are coregulated with vasopressin. In this study neuropeptide FF and another RF-amide peptide, the prolactin-releasing peptide mRNA levels were studied by quantitative in situ hybridization after chronic salt loading, a laboratory model of chronic dehydration. The neuropeptide FF mRNA expressing cells virtually disappeared from the hypothalamic supraoptic and paraventricular nuclei after salt loading, suggesting that hyperosmolar stress downregulated the NPFF gene transcription. The neuropeptide FF mRNA signal levels were returned to control levels after the rehydration period of 7 days. No changes were observed in those medullary nuclei that express neuropeptide FF mRNA. No significant changes were observed in the hypothalamic or medullary prolactin-releasing peptide mRNA levels. Neuropeptide FF mRNA is drastically downregulated in the hypothalamic magnocellular neurons after salt loading. Other neuropeptides studied in this model are concomitantly coregulated with vasopressin: i.e. their peptide levels are downregulated and mRNA levels are upregulated which is in contrast to neuropeptide FF regulation. It can thus be concluded that neuropeptide FF is not regulated through the vasopressin regulatory system but via an independent pathway. The detailed mechanisms underlying the downregulation of neuropeptide FF mRNA in neurons remain to be clarified.

Topics: Animals; Dehydration; Drinking; Gene Expression; Hypothalamus, Anterior; Male; Neurons; Oligopeptides; Paraventricular Hypothalamic Nucleus; Rats; Rats, Sprague-Dawley; Receptors, G-Protein-Coupled; RNA, Messenger; Sodium Chloride; Solitary Nucleus; Thyrotropin-Releasing Hormone; Vasopressins

Electroconvulsive therapy (ECT) is known to stimulate subcortical brain regions and release hormones from the anterior and the posterior pituitary. To enhance the subcortical effect of ECT and the neuroendocrinological response we used high dose right unilateral ECT (RUL-ECT) in 11 depressive patients and studied its effect on the release of vasopressin, prolactin and neuropeptide FF. The RUL ECT stimulus for all studied patients was 5 times the individual seizure threshold and it led to immediate release of vasopressin in all studied patients. The release of prolactin was less uniform however in accordance with results from earlier studies. The ECT also stimulated a NPFF secretion peak that came approximately 5 min after ECT stimulus and preceded the prolactin peak. The maximal elevations in circulating vasopressin and prolactin concentrations were 680% and 950%, respectively. The neuropeptide FF concentration increased by 100% after ECT. There was a second rise in NPFF concentration at 25 min after the ECT treatment. The increases in all peptide concentrations were significant, but were not correlated with each other. The neuropeptide FF concentration returned to baseline level at 10 min and the vasopressin concentration at 25 min after ECT. The prolactin concentration remained increased during the 30 min follow up period. Our results complete earlier finding on ECT stimulated vasopressin and prolactin release and show that high intensity RUL-ECT releases neuropeptide FF into human blood. The modest rise of circulating NFFF most likely represents leakage from the CNS.

Topics: Adult; Aged; Depression; Electroconvulsive Therapy; Female; Humans; Male; Middle Aged; Oligopeptides; Prolactin; Vasopressins

Neuropeptide FF (NPFF) is a peptide with opioid modulating and cardioexcitatory effects, it is present in the central nervous system and in the periphery of several mammalian species. Using a sensitive and specific radioimmunoassay for NPFF-like immunoreactivity (NPFFir) we observed that the peptide concentration fluctuated in a pattern compatible with pulsatile secretion of the peptide in human blood. When NPFF samples were collected every 2 or 5 min for a 95 min period in healthy volunteers the basal NPFF concentration in human blood was 2.2 +/- 0.5 pg/ml and the NPFF pulses (14.6 +/- 10.6 pg/ml) represented a 526 +/- 280% increase over baseline. The NPFF pulses where short, suggesting a rapid degradation of NPFF in the circulation. We observed no twenty-four hour rhythm of NPFF in human blood when NPFF samples were taken during one day every four hours. Fluctuations in NPFF levels found in the 95 min and the 24 h studies did not correlate with plasma vasopressin levels. Our study did not support the concept that vasopressin and NPFF may be co-released from the pituitary. However, the pulsatile character of NPFF secretion in itself suggests a biologic role for neuropeptide FF in humans.

Topics: Adult; Blood Glucose; Circadian Rhythm; Female; Glucose; Humans; Insulin; Male; Middle Aged; Oligopeptides; Radioimmunoassay; Vasopressins