Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01185 (vasopressin)
 23,126 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of neuropeptide Y (NPY) on LHRH release from an immortalized cell line were investigated using a flow-through cell culture superfusion system. Immortalized hypothalamic GT1-7 cells were cultured for 72 h and superfused for a total of 180 min. In initial experiments, discrete 5-min pulses of NPY (10(-12)-10(-5) M) were administered to the cells. A clear dose-dependent stimulatory effect on NPY on LHRH release from the cells was observed with a calculated 50% effectiveness concentration of 33 nM. The stimulatory effects of brief NPY exposure were rapid and robust, e.g. reaching and maintaining levels of 173% over baseline for 20 min at the 10(-7) dose. The lowest dose of NPY that showed a significant effect was 10(-10) M; maximal responses were observed at 10(-6) M and reached a plateau thereafter. Control pulses of Dulbecco's modified Eagle's medium (DMEM) and 10(-6) M substance P or arg-vasopressin were also presented to the cells to serve as controls for our pulse protocol, and these challenges produced no significant LHRH responses. The NPY receptor antagonists, PYX1 and PYX2, at 10(-8) M, completely blocked the observed NPY responses in these cells. To assess the NPY receptor subtypes that mediate the NPY effects pharmacologically, GT1-7 cells were challenged with a Y1 receptor agonist, (Leu31Pro34)NPY, a Y2 receptor agonist, NPY(13-36), or peptide YY, at doses 10(-12)-10(-5) M. All four peptides stimulated LHRH release from GT1-7 cells with a rank-ordered potency of NPY = peptide YY > Y1 agonist = Y2 agonist. To examine possible signal transduction mechanism(s) involved in mediating this effect, pertussis toxin, RpcAMPs (cyclic adenosine-3'5'-monophosphothioate Rp diastereomer), Ca(2+)-free DMEM and TMB-8 (3, 4, 5-trimethoxybenzoic acid 8-(diethylamino) octylester) were used to treat the cells before and during superfusion with NPY. Treatment with pertussis toxin, RpcAMPs, and Ca(2+)-free DMEM did not significantly alter NPY-stimulated LHRH release responses to 10(-7) M NPY. However, the addition of 100 microM and 250 microM TMB-8 to Ca(2+)-free DMEM almost completely blocked this NPY effect, as did 10 microM ryanodine. Finally, the locus of action for this NPY effect was examined using tetrodotoxin to reduce action potential propagation in the GT1-7 cells. Tetrodotoxin treatment blocked the LHRH response to NPY by more than 50%.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Neuropeptide Y stimulates luteinizing hormone-releasing hormone release from superfused hypothalamic GT1-7 cells. 792 25

In situ hybridization was used to map cellular patterns of gene expression for facilitative glucose transporters (GTs) 1-5 in the developing and adult rat kidney. GT3 was not detected. GT1 mRNA was present in the proximal straight tubule (PST), distal nephron and collecting duct. GT2 mRNA was localized in both proximal convoluted and PST, while GT5 mRNA was detected only in the PST. GT4 mRNA and immunoreactivity were focally localized in the thick ascending limb of Henle's loop and were coexpressed with IGF-I. Thus, each of the four different isoforms demonstrated a distinct renal distribution, with GTs 1, 2, and 5 coexpressed in the PST. Renal GT1 and GT5 gene expression were unchanged throughout development, while GT2 was most abundant before weaning and GT4 was first detected after weaning. Only GT4 appeared to be hormonally regulated: It was decreased after hypophysectomy and increased after vasopressin treatment, but was not affected by 1 or 4 d of insulinopenic diabetes mellitus. The coexpression of GT4 and IGF-I in the thick ascending limb segment of the nephron suggests a novel autocrine/paracrine mechanism by which cells may control local fuel economy independently from that of the larger structure to which they belong and from the systemic hormonal milieu.
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PMID:Anatomical and developmental patterns of facilitative glucose transporter gene expression in the rat kidney. 847 19

Endothelins (ETs) were initially thought to be primarily involved in the control of cardiovascular activity, but the presence of ETs and their receptors in a wide variety of other tissues has suggested a much broader range of functions. Specific receptors for ETs are found in nonvascular tissues including neuronal, neuroendocrine, and endocrine cells. In addition, immunoreactive ETs are present in the brain, pituitary, and peripheral endocrine tissues. However, the ET levels in hypothalamo-hypophysial portal and peripheral blood are low, suggesting that the ET system participates in neuroendocrine regulation through paracrine and/or autocrine mechanisms. Both ETA and ETB receptors are expressed in the hypothalamus, adrenal, parathyroid glands, pancreas, ovary, uterus, placenta, and prostate, while only ETA receptors are expressed in GT1 neurons, anterior pituitary cells, alpha T3-1 immortalized gonadotropes, parathyroid-derived cells, thyrocytes, testicular Leydig and Sertoli cells, normal and neoplastic ovarian granulosa cells, chondrocytes, and other cell types. Activation of ET receptors elicits the sequence of cellular events typical of Ca(2+)-mobilizing receptors, with prominent increases in phosphoinositide hydrolysis and elevations of [Ca2+]i that occur in oscillatory and nonoscillatory modes depending on the cell type. ET-induced activation of the phosphoinositide/Ca(2+)- mobilizing pathway in neuronal and endocrine cells is associated with rapid stimulation of secretory responses, including release of gonadotropin-releasing hormone, oxytocin, vasopressin, substance P, atrial natriuretic peptides, gonadotropins, thyrotropin, growth hormone, parathyroid hormone, aldosterone, and catecholamines. On the other hand, ET has inhibitory actions on prolactin, progesterone, and renin release. In addition to stimulating phospholipase C-dependent pathways, ETs also activate phospholipase D-and MAP-kinase-dependent pathways in some of their target cells, as well as expression of early response genes and increased mitogenic activity. In many neuroendocrine cells, ET induces rapid and marked desensitization of its signaling system, in association with extensive internalization of ET receptors and reduced signaling and secretory responses. These findings raise the possibility that ETs participate in the control of secretory responses in the hypothalamo-pituitary system and peripheral endocrine cells, as well as in long-term aspects of regulation in certain neuroendocrine cells.
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PMID:Expression and signal transduction pathways of endothelin receptors in neuroendocrine cells. 881 99

The first objective of this study was to determine whether insulin-induced hypoglycemia (IIH) inhibits LH secretion in unrestrained female macaques during the follicular phase of the menstrual cycle. There was a consistent inhibitory effect of hypoglycemia on LH secretion within 3 h in these females. This inhibition was likely an indirect effect since low glucose levels did not inhibit GnRH secretion from GT1-1 neurones in vitro. We next investigated whether administration of a vasopressin antagonist (AVPa) either alone, or with naloxone could reverse the IIH-induced inhibition of LH release. Females were studied in the follicular phase during 10 h periods with blood samples collected every 10 min. Experimental groups were IIH (n=6), IIH+AVPa (n=5) and IIH+AVPa+naloxone (n=4). The first 5 h of each study served as a control and hypoglycemia was then induced with insulin. The AVPa was given as a bolus (180 microg) just before the insulin and was followed by a continuous infusion (180 microg/h) for 5 h. Naloxone (5 mg/kg) was given with the AVPa and followed by a continuous infusion (5 mg/kg/h) for 5 h. In the IIH group, LH reached its lowest value 3-4 h after insulin. Neither AVPa nor AVPa+naloxone infusion reversed the inhibitory action of hypoglycemia on LH release. These data suggest that if there are inhibitory actions of vasopressin and endogenous opioids on GnRH release induced by hypoglycemia, they are not sufficient to explain the suppression of GnRH/LH release in intact female primates.
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PMID:Hypoglycemia-induced suppression of luteinizing hormone (LH) secretion in intact female rhesus macaques: role of vasopressin and endogenous opioids. 1218 89

Heme oxygenase (HO), the main enzyme deputed to heme metabolism, has been identified as two main isoforms called HO-1 and HO-2. HO-1 is inducible and plays a main role in the cellular oxidant/antioxidant balance whereas HO-2 is constitutive and involved in the physiological metabolism of heme. However, it is noteworthy to mention that HO contribute to the regulation of the hypothalamic release of neuropeptides such as corticotrophin-releasing hormone and arginine-vasopressin and could modulate the pulsatile release of gonadotropin releasing hormone (GnRH). GT1-7 cells are immortalized hypothalamic neurons and a valuable tool to evaluate hypothalamic neuroendocrine control of reproduction. The aim of this work was to investigate and characterize the presence of HO isoforms in the GT1-7 hypothalamic neurons. Hemin, a well-known inducer of HO-1, significantly increased HO activity, whereas dexamethasone did not modify HO-2 activity. Moreover, hemin and DEX, in combination, did not have any additive effect on HO activity in GT1-7 neurons. Furthermore, basal HO-1 immunoreactivity identified in GT1-7 cells, was significantly up-regulated by hemin. Conversely, no HO-2 immunoreactivity was detected. Taken together, these results suggest the presence of functional HO-1 in GT1-7 immortalized hypothalamic neurons and open new avenues about the use of this cell line for the study of HO modulation of GnRH secretion and reproduction.
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PMID:Heme oxygenase expression and activity in immortalized hypothalamic neurons GT1-7. 1870 74

Heme oxygenase (HO), the main enzyme deputed to heme metabolism, has been identified as two main isoforms called HO-1 and HO-2 both present in the central nervous system. Heme oxygenase has been shown to regulate the hypothalamic release of neuropeptides such as corticotrophin-releasing hormone and arginin-vasopressin. The aim of this study was to investigate and further characterize the presence of HO in gonadotropin-releasing hormone (GnRH) secreting hypothalamic neurons, GT1-7 and the role of HO by-products on GnRH secretion. The pulsatile release of GnRH from scattered hypothalamic neurons is the key regulator of mammalian fertility in the central nervous system. GT1-7 cells are immortalized hypothalamic neurons, characterized by spontaneous electrical activity and pulsatile GnRH release, resembling the central control pathway of the hypothalamic pituitary gonadal axis (HPG) in mammals. Hemin, the substrate of HO, significantly stimulated HO activity in static cultures, causing a rapid increase in GnRH release. Neither biliverdin nor bilirubin were able to mimic this rapid stimulatory effect, which was instead caused by carbon monoxide. Evidence of a possible involvement of prostaglandin E(2) in the HO by-product modulated GnRH secretion was reported. The hemin-evoked effect on GT1-7 neurons suggests a direct activity of HO by-products on the hypothalamic neuropeptide secretion, and claims for a possible role of CO in both the modulation of gonadotropin secretion and crosstalk among HPG and stress axis within the mammalian hypothalamus.
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PMID:Heme oxygenase-derived carbon monoxide modulates gonadotropin-releasing hormone release in immortalized hypothalamic neurons. 2009 64