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 topographical distribution of neuropeptide-containing cell bodies, fibers and terminals was studied in the premamillary region of the rat hypothalamus using light microscopic immunohistochemistry. Alternate coronal sections through the posterior third of the hypothalamus of normal and colchicine-treated male rats were immunostained for 19 different neuropeptides and their distributions were mapped throughout the following structures: the ventral and dorsal premamillary, the supramamillary, the tuberomamillary and the posterior hypothalamic nuclei, as well as the premamillary portion of the arcuate nucleus and the postinfundibular median eminence. Seventeen of the investigated neuropeptides were present in neuronal perikarya, nerve fibers and terminals while the gonadotropin associated peptide and vasopressin occurred only in fibers and terminals. Growth hormone-releasing hormone-, somatostatin-, alpha-melanocyte stimulating hormone-, adrenocorticotropin-, beta-endorphin- and neuropeptide Y-immunoreactive neurons were seen exclusively in the premamillary portion of the arcuate nucleus. Thyrotropin-releasing hormone-, dynorphin A- and galanin-containing neurons were distributed mainly in the arcuate and the tuberomamillary nuclei. A high number of methionine- and leucine-enkephalin-immunoreactive cells were detected in the arcuate and dorsal premamillary nuclei, as well as in the area ventrolateral to the fornix. Substance P-immunoreactive perikarya were present in very high number within the entire region, in particular in the ventral and dorsal premamillary nuclei. Cell bodies labelled with cholecystokinin- and calcitonin gene-related peptide antisera were found predominantly in the supramamillary and the terete nuclei, respectively. Corticotropin-releasing hormone-, vasoactive intestinal polypeptide- and neurotensin-immunoreactive neurons were scattered randomly in low number, mostly in the arcuate and the ventral and dorsal premamillary nuclei. Peptidergic fibers were distributed unevenly throughout the whole region, with each peptide showing an individual distribution pattern. The highest density of immunoreactive fibers was presented in the ventral half of the region including the arcuate, the ventral premamillary and the tuberomamillary nuclei. The supramamillary nucleus showed moderately dense fiber networks, while the dorsal premamillary and the posterior hypothalamic nuclei were poor in peptidergic fibers.
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PMID:Immunohistochemical mapping of neuropeptides in the premamillary region of the hypothalamus in rats. 779 57

Amyotrophic lateral sclerosis (ALS) is a chronic neurodegenerative disorder of the motor system in the CNS characterized by motor neuron death in the spinal cord, brain stem and cortex. Readily available tissues such as fibroblasts from ALS patients can serve as simple model systems to study the molecular mechanisms leading to degenerative disorders. We have used Fura-2 fluorescence microscopy and single-cell imaging to study the spatiotemporal dynamics of intracellular free calcium ([Ca2+]i) in primary cultures of fibroblasts from skin biopsies from ALS and normal subjects. Increases in [Ca2+]i were induced by stimulation with bradykinin (100 nM); neurotensin (50 nM); N-formyl-Met-Leu-Phe (chemotactic peptide) (1 microM); [Arg8]-vasopressin (1 microM) and histamine (10 microM). The levels of [Ca2+]i in 80-120 individual cells per agonist were monitored for 15 min. No significant differences were found in the resting levels of [Ca2+]i in control (102 +/- 4 nM) and ALS (98 +/- 6 nM) fibroblasts and in the maximal [Ca2+]i levels after stimulation with N-formyl-Met-Leu-Phe, [Arg8]-vasopressin, and histamine. Significantly lower [Ca2+]i transients were found in fibroblasts from ALS donors compared to controls when stimulated with neurotensin (p < 0.002) and bradykinin (p < 0.005). The percentage of individual cells reacting to a given agonist (40-100%) was similar in both groups. The molecular basis of the impaired calcium homeostasis in fibroblasts from ALS patients is not known, but a generalized membrane defect can be excluded since the [Ca2+]i responses are defective only when bradykinin or neurotensin are used as agonists.
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PMID:Calcium homeostasis in fibroblasts from patients with amyotrophic lateral sclerosis. 785 28

Morphological and pharmacological evidence suggest that the dense GABAergic innervation of the supraoptic nucleus is important for regulating the electrical activity of vasopressin and oxytocin neurons. We have employed the technique of intracranial microdialysis to examine extracellular GABA concentrations in the supraoptic nucleus of the anaesthetized rat and questioned whether differences exist in the dynamics of GABA release between virgin and lactating rats, and if events during lactation or following blood pressure manipulation alter endogenous GABA levels in this nucleus. No significant differences were detected between virgin and lactating animals in either basal or 100 mM potassium ion-evoked GABA release. The inclusion of the GABA uptake blocker nipecotic acid (0.5 mM) into the dialysate resulted in a six- to eight-fold increase (P < 0.01) in GABA outflow in both groups of animals. In lactating rats, GABA outflow measured at 4 min intervals was not altered during a 60 min period of suckling by a full litter of pups and no significant change in GABA outflow was detected in relation to individual milk ejections. In virgin rats, removal of 1.5-2 ml of blood resulted in a 30-60 mmHg fall in blood pressure and a non-significant decline in GABA outflow. Replacement of blood resulted in an abrupt 50 mmHg increase in blood pressure and a significant 22% increase in GABA outflow (P < 0.01), but no change in aspartate or methionine concentrations. Repeated intravenous injections of the alpha-adrenoceptor agonist, metaraminol, similarly evoked approximately 50 mmHg increments in blood pressure and a 26% increase in GABA outflow (P < 0.05). Electrical stimulation of the diagonal band of Broca for 10 min produced a two-fold increase in GABA outflow from the supraoptic nucleus (P < 0.05). These results show that the overall profile of basal and potassium-stimulated GABA concentrations in the supraoptic nucleus is not substantially different between lactating and virgin rats. In lactating animals we have found that GABA levels are not altered in response to suckling or at the time of high-frequency firing by oxytocin neurons to induce milk ejection. In contrast, our data further support the hypothesis that GABA inputs to supraoptic neurons are part of a baroreceptor reflex, relaying through the diagonal band of Broca, to signal periods of acute hypertension and inhibit the firing of vasopressin neurons. Such observations suggest the physiological importance of GABA inputs to the supraoptic nuclei and indicate that GABA may be used in a stimulus-specific manner to influence the activity of magnocellular neurons.
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PMID:Extracellular GABA concentrations in rat supraoptic nucleus during lactation and following haemodynamic changes: an in vivo microdialysis study. 789 64

Previous studies have suggested an involvement of enkephalins in regulation of oxytocin (OXT) and vasopressin (AVP) release, which seems to disagree with the very low affinities of Met- and Leu-enkephalin for the kappa opioid receptor. As opioid receptors in the neural lobe exclusively exist of kappa receptors, we studied the binding characteristics of larger pro-enkephalin derived peptides for opioid binding sites in the neural lobe by means of light microscopic receptor autoradiography. In addition, the pharmacological characteristics of opioid binding sites in the neural lobe were compared with those in other parts of the pituitary. In the neural as well as the intermediate lobe both high and low affinity 3H-bremazocine binding sites were present. Binding to these sites was completely displaceable by both naloxone and nor-binaltorphimine suggesting that these sites represent kappa opioid receptors. Also with regard to selectivity and affinity characteristics to other ligands, opioid binding sites in the neural and intermediate lobe were quite similar. In the anterior lobe a very low level of bremazocine binding was present, which could not be displaced by nor-binaltorphimine. Displacement studies with pro-enkephalin and pro-dynorphin derived peptides showed that both groups of peptides could bind to opioid binding sites in the neural and intermediate lobe. Especially the relatively large pro-dynorphin and pro-enkephalin derived peptides, such as dynorphin 1-17 and BAM22, appeared to be very potent ligands for these opioid binding sites and were much more potent than smaller fragments, such as dynorphin 1-8, and Met- and Leu-enkephalin. These results contradict the existence of a mismatch in the neural (and intermediate) lobe with regard to the local type of opioid peptides and receptors present.
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PMID:Characterization of opioid binding sites in the neural and intermediate lobe of the rat pituitary gland by quantitative receptor autoradiography. 802 68

The nucleus tractus solitarii (NTS), which receives visceral afferent information from the cardiovascular, respiratory, gastrointestinal and taste systems, contains multiple neurotransmitters and neuropeptides throughout its rostral to caudal extent. The neurotransmitters and neuropeptides immunoreactivity is located predominately in varicose fibers and small puncta throughout the neuropil. In addition, immunoreactive NTS neurons for a variety of neurotransmitters and neuropeptides are present in subnuclear regions. The neuroactive substances localized immunohistochemically in the NTS include acetylcholine, the neuropeptides, substance P, methionine- and leucine-enkephalin, beta-endorphin, cholecystokinin, neurotensin, galanin, calcitonin gene-related peptide, somatostatin, FMRMamide, neuropeptide Y, angiotensin II, vasoactive intestinal polypeptide, vasopressin, oxytocin, thyrotropin-releasing hormone, luteinizing hormone-releasing hormone, atrial natriuretic peptide, the catecholamines, dopamine, norepinephrine, epinephrine, serotonin, histamine and the amino acids, GABA and glutamate. The pattern of innervation for each neurotransmitter and neuropeptide is not homogeneously distributed throughout the NTS. Each substance has a unique pattern within the NTS as each subnuclear region contains different immunohistochemical staining patterns and densities of fibers. At the ultrastructural level both neurotransmitters and neuropeptides are present in synaptic terminals that are in contact with different parts of the neuronal membranes. Typically, the labeled terminals contain both small, clear vesicles and large, dense core vesicles with the exception of synaptic terminals containing acetylcholine, GABA and glutamate which do not typically have the large, dense core vesicles. The most frequent post-synaptic target are dendrites and spinous processes. Less frequently, synaptic contacts are present on the cell soma.
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PMID:Immunohistochemical localization of neuropeptides and neurotransmitters in the nucleus solitarius. 867 Jul 16

Mouse neuroblastoma Neuro-2a cells were examined for the expression of pro-enkephalin mRNA, protein, and Met-enkephalin ([Met]-Enk) peptide. Reverse transcriptase/polymerase chain reaction (RT/PCR) and in situ hybridization demonstrated the presence of pro-enkephalin mRNA in these cells. Immunocytochemistry using an antibody which recognizes pro-enkephalin and high pressure liquid chromatography (HPLC) followed by radioimmunoassay indicated that pro-enkephalin was synthesized in these cells and processed to yield the bioactive pentapeptide, [Met]-Enk. Furthermore, release studies showed that the [Met]-Enk was secreted from these cells with high K+ stimulation. Using double labeling, in situ hybridization combined with immunocytochemistry, we demonstrated that prohormone convertase 2 (PC2) mRNA is colocalized with pro-enkephalin in the same Neuro-2a cells, suggesting that this enzyme may be responsible for processing this precursor. we also showed the presence of vasopressin mRNA and arginine-vasopressin peptide in these cells using in situ hybridization and immunocytochemistry, respectively. Thus, the Neuro-2a cells are a multiple neuropeptide-producing cell line and an excellent model for studying the mechanisms involved in the synthesis, intracellular targeting and processing of endogenous pro-enkephalin and pro-vasopressin, as well as other transfected neuropeptide precursors.
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PMID:The Neuro-2a neuroblastoma cell line expresses [Met]-enkephalin and vasopressin mRNA and peptide. 867 23

The amiloride-sensitive epithelial Na+ channel is formed by the assembly of three homologous subunits, alpha, beta and gamma. The channel is characterized by its sensitivity to amiloride and to some amiloride derivatives, such as phenamil and benzamil, by its small unitary conductance (approximately 5 pS), by its high selectivity for lithium and sodium, and by its slow kinetics. The alpha-, beta-, and gamma-proteins share significant identity with degenerins, a family of proteins found in the mechanosensory neurons and interneurons of the nematode Caenorhabditis elegans. They are also homologous to FaNaCh, a protein from Helix aspersa nervous tissues, which corresponds to a neuronal ionotropic receptor for the Phe-Met-Arg-Phe-NH2 peptide. All these proteins contain a large extracellular loop, located between two transmembrane alpha-helices. The NH2 and COOH terminal segments are cytoplasmic and contain potential regulatory segments that are able to modulate the activity of the channel. Accordingly, in Liddle syndrome, in which patients develop a form of genetic hypertension, mutations within the cytoplasmic COOH terminal of the beta- and gamma-chains of the epithelial Na+ channel lead to a hyperactivity of the channel. Epithelial Na+ channel activity is tightly controlled by several distinct hormonal systems, including corticosteroids and vasopressin. In kidney and colon, aldosterone is the major sodium-retaining hormone, acting by stimulation of Na+ reabsorption through the epithelium. In the distal colon from steroid-treated animals, a large increase in beta- and gamma-subunit transcription is observed, whereas the alpha-subunit remains constitutively transcribed. In kidney, RNA levels of the three subunits are not altered by aldosterone, suggesting that other mechanisms control Na+ channel activity in that tissue. In lung, the glucocorticoids are positive regulators of the channel activity, especially around birth, and act via an increased transcription of the three subunits.
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PMID:Molecular biology of the amiloride-sensitive epithelial Na+ channel. 873 81

It has been observed that a vasopressin receptor antagonist attenuates hypoxic hyperemia in fetal sheep, whereas methionine enkephalin (Met) and leucine enkephalin (Leu) contribute to hypoxia-induced pial artery dilation in newborn pigs. This study was designed to investigate the relationship between vasopressin and opioids in hypoxia-induced pial artery dilation in the newborn pig by use of the closed cranial window technique. Hypoxia-induced pial artery dilation was attenuated during moderate [arterial Po2 (PaO2) approximately 35 mmHg] and severe hypoxia (PaO2 approximately 25 mmHg) by the vasopressin receptor antagonist, [beta-mercapto-beta beta-cyclopentamethylenepropionyl, 2-O-Me-Tyr2, Arg8]vasopressin (MeAVP, 5 micrograms/kg i.v.; 29 +/- 1 vs. 14 +/- 2 and 37 +/- 2 vs. 18 +/- 2% for moderate and severe hypoxia in absence vs. presence of MeAVP, respectively, n = 7). Hypoxia-induced dilation was accompanied by increased cerebrospinal fluid (CSF) vasopressin concentration (26 +/- 1 vs. 67 +/- 4 and 26 +/- 1 vs. 99 +/- 4 pg/ml for control vs. moderate and control vs. severe hypoxia, n = 5). Vasopressin increased CSF Met (895 +/- 28, 1,147 +/- 63, 1,327 +/- 48, and 1,600 +/- 75 pg/ml for control and 40, 400, and 4,000 pg/ml vasopressin, respectively, n = 7). CSF Leu concentration was similarly increased by vasopressin. Furthermore, MeAVP attenuated the release of Met during moderate hypoxia (910 +/- 38 and 2,682 +/- 49 vs. 911 +/- 38 and 2,110 +/- 84 pg/ml for control and moderate hypoxia in absence and presence of MeAVP, respectively, n = 5). MeAVP had similar effects on hypoxia-induced Leu release. These data show that vasopressin contributes to hypoxia-induced pial artery dilation and that vasopressin increases CSF Met and Leu concentrations. These data also suggest that elevated CSF vasopressin concentrations that occur during hypoxemia result in opioid release, which subsequently contributes to hypoxic pial artery dilation.
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PMID:Relationship between vasopressin and opioids in hypoxia induced pial artery vasodilation. 877 92

The terminal nerve is a ganglionated cranial nerve with peripheral processes that enter the nasal cavity and centrally directed processes that enter the forebrain. Members of all classes of gnathostomes have been found to possess a terminal nerve, some components of which demonstrate immunoreactivity to the peptides Phe-Met-Arg-Phe-NH2 (FMRFamide) and gonadotropin-releasing hormone (GnRH). To explore the possibility that lampreys possess a terminal nerve, we examined the distribution of these peptides in the silver lamprey, Ichthyomyzon unicuspis, by using antisera to FMRFamide and to four forms of GnRH. We found cells with FMRFamide-like immunoreactivity in the preoptic area and the isthmal gray region of the mesencephalon, and found labeled fibers throughout the preoptic-infundibular region. Occasional labeled fibers were scattered through many regions of the brain, including the optic nerve and olfactory bulb; however, unlike species that possess a terminal nerve, lampreys have no immunoreactive cells or fibers in the olfactory nerve or nasal epithelia. In addition, we observed GnRH-immunoreactive cell bodies in the preoptic area of all animals and in the ventral hypothalamus of one individual. Most of the labeled fibers extended ventrally to the hypothalamus, with other fibers extending throughout the striatum and hypothalamic-neurohypophyseal region. A few fibers in other regions, including the optic nerve, were also labeled; we detected no immunoreactivity in the olfactory bulb, olfactory nerve, or nasal epithelia. The use of different GnRH antisera resulted in remarkably similar patterns of labeling of both cells and fibers. In summary, we did not observe either GnRH or FMRFamide-like immunoreactivity in the olfactory regions that represent the typical path of terminal nerve fibers, nor were we able to locate a terminal nerve ganglion. We conclude that lampreys may lack a terminal nerve, and that the previously described fiber bundle extending from the nasal sac to the ventral forebrain may constitute an extra-bulbar olfactory pathway.
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PMID:Silver lampreys (Ichthyomyzon unicuspis) lack a gonadotropin-releasing hormone- and FMRFamide-immunoreactive terminal nerve. 880 28

We have synthesized eight analogues of the linear vasopressin antagonist DTyr(Et)2-Phe3-Gln4-Asn5-Arg6-Pro7-Arg8-Tyr(NH2)9 substituted with L-, or D-, pyroglutamate at position-1, Asn or Val at position-4 and Arg or Met at position 6. All of these peptides bound to the V1a vasopressin receptor with affinities ranging 33.6-5, 470 nM. Of this series, only two peptides, [LpGlu1Val4Arg6Tyr(NH2)9]AVP Kd = 48.4 nM and [DpGlu1Val4Arg6Tyr(NH2)9]AVP Kd = 691 nM, bound to the V2 vasopressin receptor. All of the neurohypophysial hormone receptors studied (V1a VPR, V2 VPR and OTR) were found to be stereoselective with respect to the N-terminal pGlu residue. The effect on binding characteristics of L-pGlu1 and D-pGlu1 analogues was dependent on both the sequence of the peptide and on the receptor subtype in question. From these data we found that peptide 5, which has the structure DpGlu-DTyr(Et)-Phe-Val-Asn-Arg-Pro-ARg-Tyr(NH2), exhibited the highest V1a/OTR selectivity reported to date (V1aVPR Kd = 82 nM; OTR no binding at 10 microM). As such, peptide 5 will provide useful leads to the development of ligands with enhanced V1a/OTR selectivity. The binding affinity and hydrophobicity of pyroglutamate-substituted peptides was compared with previously characterized V1a receptor antagonists which contained a range of position-1 substitutions. The hydrophobicity of both cyclic and linear antagonists was markedly increased relative to the agonists AVP and [Phe2Orn8]VT but increased hydrophobicity alone did not exclusively lead to high affinity antagonists. Data presented support the contention that in addition to a general increase in hydrophobicity/lipophilicity, position-1 influences the pharmacophore of vasopressin antagonists by providing molecular determinants for ligand/receptor interaction.
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PMID:Probing the V1a vasopressin receptor binding site with pyroglutamate-substituted linear antagonists. 886 3


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