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At least 55 records · Page 3Linked to original sources
PubMed1975

Identification of neurophysin producing cells. III. Immunohistochemical demonstration of neurophysin I-producing neurons in the bovine infundibular nucleus.

Immuno-enzyme histochemical investigations on the bovine hypothalamus showed that the infundibular nucleus contains neurons that produce either neurophysin I or a neurophysin I-like substance. Fine processes of these neurons run in the direction of the median eminence. The possibility that these processes could be the origin of the "neurophysin I-oxytocin" containing nerve fibres of the external region of the median eminence is discussed.

Animals↗
PubMed1985

Use of perdeuterated peptides in NMR studies of neurophysin-hormone interaction: demonstration of peptide-specific changes in neurophysin resonances.

The effects on bovine neurophysin-I of binding the perdeuterated peptides Phe-PheNH2 and Leu-PheNH2 were compared by proton NMR. A unique difference between the two peptides in their effects on Tyr-49 ring protons indicated proximity of the Tyr-49 ring to the side-chain of position 1 of bound peptide. Non-deuterated oligopeptides containing Phe in position 3 and no methyl groups induced different changes in neurophysin methyl resonances than dipeptides, suggesting shielding of one or more protein methyl groups by Phe-3. The results demonstrate that the identity of neurophysin residues at the hormone-binding site can be probed by analysis of changes induced in the protein spectrum by systematically related NMR-transparent peptides.

Binding Sites↗
PubMed1980

Synthesis of peptide spin-labels that bind to neurophysin and their application to distance measurements within neurophysin complexes.

The synthesis of two spin-labels capable of binding to the hormone-binding site(s) of neurophysin is described. The two spin-labels are 4-(glycyl-L-phenylalanylamido)-2,2,6,6-tetramethylpiperidinyl-1-oxy and S-[[[3-(2,2,5,5-tetramethylpyrrolidine-1-oxy)amino]carbonyl]methyl]-L-cysteinyl -L-tyrosine amide; synthesis of the former is achieved by a novel route to circumvent problems associated with nitroxide instability under standard conditions of peptide deblocking. NMR studies of the effects of binding these spin-labels on relaxation rates of individual proton resonances of neurophysin were used to calculate correlation times and distances between the bound nitroxides and the observed protons. The results indicate that residue 3 of peptides bound to the strong site of neurophysin is greater than or equal to 14 A from Tyr-49 and argue against a distance of < 5 A between the ortho ring protons of Tyr-49 and those of residue 2 of peptides bound to the strong site. Alternatively, the data suggest that the previously observed nuclear Overhauser effect between these protons reflects spin diffusion at the strong site and a contribution of uncertain magnitude from a second but very weak binding site; this second site is close to Tyr-49 and is detected by the increased relaxation rate of Tyr-49 ring protons when 4-(glycyl-L-phenylalanylamido)-2,2,6,6-tetramethylpiperidinyl-1-oxy is displaced from the strong site by competing diamagnetic peptide. Additionally, the data indicate that residue 3 of bound peptides at the strong site is distant from His-80 but approximately 12 A from the amino terminus. The extended side chain of residue 1 of peptides at the strong site is calculated as less than or equal to 10 A from Tyr-49.

Animals↗
PubMed2001

Autosomal dominant neurohypophyseal diabetes insipidus in a Swiss family, caused by a novel mutation (C59Delta/A60W) in the neurophysin moiety of prepro-vasopressin-neurophysin II (AVP-NP II).

OBJECTIVE: To study clinical, morphological and molecular characteristics in a Swiss family with autosomal dominant familial neurohypophyseal diabetes insipidus (adFNDI). PARTICIPANTS AND METHODS: A 15-month-old girl presenting with symptoms of polydipsia and polyuria was investigated by water deprivation test. Evaluation of the family revealed three further family members with symptomatic vasopressin-deficient diabetes insipidus. T1-weighted magnetic resonance images of the posterior pituitary were taken in two affected adult family members and molecular genetic analysis was performed in all affected individuals. RESULTS: The water deprivation test in the 15-month-old child confirmed the diagnosis of vasopressin-deficient diabetes insipidus and the pedigree was consistent with autosomal dominant inheritance. The characteristic bright spot of the normal vasopressin-containing neurophypophysis was absent in both adults with adFNDI. Direct sequence analysis revealed a new deletion (177-179DeltaCGC) in exon 2 of the AVP-NP II gene in all affected individuals. At the amino acid level, this deletion eliminates cysteine 59 (C59Delta) and substitutes alanine 60 by tryptophan (A60W) in the AVP-NP II precursor; interestingly, the remainder of the reading frame remains unchanged. According to the three-dimensional structure of neurophysin, C59 is involved in a disulphide bond with C65. CONCLUSIONS: Deletion of C59 and substitution of A60W in the AVP-NP II precursor is predicted to disrupt one of the seven disulphide bridges required for correct folding of the neurophysin moiety and thus disturb the function of neurophysin as the vasopressin transport protein. These data are in line with the clinical and morphological findings in the reported family with adFNDI.

Amino Acid Sequence↗
PubMed1976

Immunohistological identification of neurophysin and neurophysin-like substances in different vertebrates.

Using rabbit antisera to porcine neurophysin, the immunohistological unlabelled-antibody-peroxidase technique was applied to brains of man, rat, quail, pigeon, tortoise, frog, two cyprinid fishes, sturgeon and lamprey as well as to the urophysis of carp and the brain of the cockroach. In each of the investigated vertebrate speices the magnocellular neurosecretory system is immunoreactive, known to give a specific reaction for neurosecretory material by means of appropriate histological and histochemical methods, too. Moreover, in the rat brain we found immunoreactive material in neurons of the suprachiasmatic nucleus, in the parvocellular part of the paraventricular nucleus, in fibres of the external region of the median eminence and in neurosecretory exohypothalamic fibres. The subcommissural organ and Reissner's fibre as well as the urophysis of the fish spinal cord and neurosecretory cells of the insect brain are devoid of neurophysin or neurophysin-like substances.

Aged↗
PubMed1971

Tentative identification of a vasopressin-neurophysin and an oxytocin-neurophysin in the rat.

1. Rat neurohypophysial extracts have been examined by polyacrylamide-gel electrophoresis. 2. Three of the proteins were tentatively identified as neurophysins by their acidic nature and their disappearance after dehydration of the animals. 3. These proteins were radioactive 24h after intracisternal injection of [(35)S]cysteine. 4. Two of the proteins were present in much greater quantities than the third, and these two were present in the gland in the same ratio as the hormones vasopressin and oxytocin. 5. One of these proteins was absent from glands of rats homozygous for diabetes insipidus but present in heterozygous animals. 6. It is suggested that these two proteins are the vasopressin-neurophysin and oxytocin-neurophysin of the rat.

Animals↗
PubMed1993

The pituitary hormones arginine vasopressin-neurophysin II and oxytocin-neurophysin I show close linkage with interleukin-1 on mouse chromosome 2.

Arginine vasopressin (AVP) and oxytocin (OXT) are posterior pituitary hormones. AVP is involved in fluid homeostasis, while OXT is involved in lactation and parturition. AVP is derived from a larger precursor, pre-pro-arginine-vasopressin-neurophysin II (prepro-AVP-NP II; AVP), and is physically linked to prepro-oxytocin-neurophysin I (prepro-OXT-NP I; OXT). The genes for AVP and OXT are separated by only 12 kb of DNA in humans, whereas in the mouse 3.5 kb of intergenic sequence lies between Avp and Oxt. Interspecific backcross analysis has now been used to map the Avp/Oxt complex to chromosome 2 in the mouse. This map position confirms and extends the known region of linkage conservation between mouse chromosome 2 and human chromosome 20.

Animals↗
PubMed1999

A novel mutation (R97C) in the neurophysin moiety of prepro-vasopressin-neurophysin II associated with autosomal-dominant neurohypophyseal diabetes insipidus.

Autosomal-dominant familial neurohypophyseal diabetes insipidus (adFNDI) is caused by heterozygous mutations in the gene encoding vasopressin-neurophysin II (AVP-NPII) on chromosome 20p13. We analyzed the AVP-NP II gene in a family with adFNDI by direct sequencing. A novel C to T transition (289C-->T in the cDNA, resulting in the substitution of Arg 97 by Cys (R97C) in the prepro-AVP-NPII precursor molecule) was identified in the gene region encoding neurophysin II in the index patient. This amino acid change is thought to result in the formation of an incorrectly folded hormone precursor, which may lead to chronic neurotoxicity and explain the dominant inheritance of the disease.

Arginine Vasopressin↗
PubMed1976

Electron microscopic immunocytochemical demonstration of separate neurophysin-vasopressinergic and neurophysin-oxytocinergic nerve fibres in the neural lobe of the rat hypophysis.

By means of the unlabeled antibody peroxidase-antiperoxidase (PAP) technique at the electron microscopic level, it was demonstrated that the hormones of the neural lobe of the rat hypophysis are located in separate neurophysin-vasopressinergic and neurophysin-oxytocinergic nerve fibres. These observations confirm the results of our previous immunocytochemical studies at the light microscopic level.

Animals↗
PubMed1988

An amphibian two-domain 'big' neurophysin: conformational homology with the mammalian MSEL-neurophysin/copeptin intermediate precursor shown by trypsin-sepharose proteolysis.

A 'big' frog (Rana esculenta) neurophysin, encompassing sequences homologous to mammalian MSEL-neurophysin and copeptin, has been passed through a trypsin-Sepharose column in order to compare its conformation with that of the two-domain intermediate precursor isolated from guinea pig. Whereas the polypeptide possesses 8 arginine residues, only two cleavages were observed located in a putative inter-domain sequence (at Arg-94 and Arg-114). Because free vasotocin has been isolated from the frog, it is assumed that pro-vasotocin has a three-domain conformation similar to that of pro-vasopressin but processing in amphibians involves only one step rather than two steps as in mammals.

Amino Acid Sequence↗
PubMed1990

Linkage relationships of human arginine vasopressin-neurophysin-II and oxytocin-neurophysin-I to prodynorphin and other loci on chromosome 20.

The structural genes for human prepro-arginine-vasopressin-neurophysin II (prepro-AVP-NPII; ARVP) locus and prepro-oxytocin-neurophysin-I (prepro-OT-NPI; OT) locus are closely linked separated by only 12 kilobasepairs of DNA. These two loci have been assigned to chromosome 20 by previous studies of somatic cell hybrids. We used Southern blots to analyze a restriction fragment length polymorphism detected by a probe for prepro-OT-NPI to determine the linkage relationships for the ARVP/OT loci using samples from the Centre d'Etude du Polymorphisme Humain (Paris, France) collection of families. The ARVP/OT loci demonstrated extremely close linkage with the prodynorphin (PDYN) locus, with no recombinants (theta of 0) and a log10 odds score of 5.2. Previous observations have shown the ARVP and PDYN peptides to be coexcreted in the same neurosecretory granules of some pituitary axons and that increased transcription of both genes occurs with osmotic stimulation. The combined ARVP/PT/PDYN group was also found to demonstrate linkage with other anonymous DNA segments on chromosome 20, including D20S4, D20S5, and D20S6. Using multilocus linkage analysis, the ARVP/OT loci map to the distal short arm of chromosome 20 about 15 centimorgans toward the telomere from the D20S5 locus, which is located near the middle of the short arm at 20p 12.21. These linkage relationships establish that the secretory and transcriptional associations of ARVP and PDYN extend to a close physical relationship in the human genome. Furthermore, the restriction fragment length polymorphism detected by these loci can serve as accurate markers in segregation studies of putative defects involving the OT, ARVP, or PDYN loci as well as provide a tool for studying the location of other genes, such as GH-releasing hormone.

Arginine Vasopressin↗
PubMed1994

Differential neurophysin immunoreactivities in solitary magnocellular neurons of the homozygous Brattleboro rat indicate an altered neurophysin moiety.

In the homozygous Brattleboro rat (di/di) a single base deletion in the vasopressin (VP) gene causes diabetes insipidus, resulting in the synthesis of a VP precursor with a different C-terminus. We reported previously that a small number of post-mitotic VP neurons in di/di rats undergo a switch to a heterozygous phenotype, suggesting the existence of VP mRNAs with a restored reading frame coding for a normal VP precursor. In the present study we report that the increase in the number of these revertant cells declines after 79 weeks of age. Furthermore, we provide evidence that the neurophysin (NP) moiety in solitary neurons is different from normal NP. Comparing the immunoreactivities of two different NP antibodies we deduced that the restoration of the reading frame may take place downstream of the deletion between amino acids 75 and 93 of the VP-NP.

Aging↗
PubMed1983

Colocalization of oxytocin and neurophysin-I/II and of vasopressin and neurophysin-III in neurons of the sheep hypothalamus. An immunohistochemical study.

Antisera raised against, oxytocin, vasopressin and ovine neurophysins-I, -II and -III (oN-I, oN-II and oN-III respectively) were used in association with the immunohistochemical procedure to stain neurons of the formalin-fixed sheep hypothalamus. Cells that stain for oxytocin also contain oN-I and oN-II and differ from those that stain for vasopressin and oN-III. The observations support our earlier findings in the sheep that oxytocin- and vasopressin-related events are accompanied by the release of oN-I/II and oN-III respectively.

Animals↗
PubMedDate not supplied

Familial central diabetes insipidus: vasopressin and nicotine stimulated neurophysin deficiency with subnormal oxytocin and estrogen stimulated neurophysin.

Five members of a family with dominantly inherited diabetes insipidus were diagnosed and treated with deamino-d-arginine vasopressin (DDAVP), a vasopressin analogue given intranasally. All subjects demonstrated subnormal levels of arginine vasopressin (AVP) by radioimmunoassay in response to cigarette smoke inhalation, a standardized nicotine stimulation test. Levels of oxytocin (OT) were found to be normal and unstimulated after cigarette inhalation in two subjects, but when two affected male siblings ingested Ovulen, OT and ESN were stimulated to subnormal levels. After twelve months of DDAVP treatment, the low AVP response to nicotine was preserved whereas the carrier protein, nicotine stimulated neurophysin (NSN) remained undetectable.

Adolescent↗
PubMed1983

Development of radioimmunoassays for ovine neurophysins. Correlation of neurophysin release with oxytocin- and vasopressin-related stimuli.

Specific homologous RIAs for the ovine neurophysins (oN-I/II, oN-III) were established; the assays had a sensitivity capable of measuring basal levels of the pituitary proteins in sheep plasma. Reduction in blood volume of ewes caused a 200-fold increase in oN-III with minimal changes in oN-I/II levels. After infusion of either hypertonic saline or nicotine, a similar specific increase in oN-III was observed, occurring at a time when the free water clearance rate decreased. Intramuscular administration of estradiol benzoate caused an increase in jugular plasma oN-I/II concentrations without affecting the oN-III concentrations. In one of six lactating ewes, there was an increase in oN-I/II during suckling. The release of oN-I/II, which was accompanied by small increases in oN-III, exhibited a pulsatile profile similar to that reported for the secretion of oxytocin under similar conditions. During vaginal distension, increases in intramammary pressure were accompanied by elevations in levels of oN-I/II and oN-III. It is concluded that oxytocin-related events are associated predominantly with the release of oN-I/II and that stimuli that induce vasopressin release also cause elevation of oN-III. These correlations are consistent with our previous conclusion from biochemical and amino acid sequence analysis of the oNs.

Amino Acid Sequence↗
PubMed2004

Identification of a novel mutation in the arginine vasopressin-neurophysin II gene affecting the sixth intrachain disulfide bridge of the neurophysin II moiety.

OBJECTIVE: Most mutations of the arginine vasopressin-neurophysin II (AVP-NPII) gene cause autosomal dominant familial neurohypophyseal diabetes insipidus (adFNDI). Such mutations are predicted to alter the three-dimensional structure of the prohormone, which accumulates in the cell body, ultimately leading to neuronal degeneration and hormonal deficit. In this study we describe the case of a 26-year-old female reporting a long-lasting history of polyuria/polydipsia. The father of the patient was affected by diabetes insipidus and was under desmopressin treatment until the time of his death. Nevertheless, the patient had never been subjected to endocrine evaluation. DESIGN AND METHODS: Clinical and genetic studies were performed. An 8-h fluid deprivation test plus desmopressin challenge and a 5% saline solution test were performed, in order to confirm the diagnosis. DNA was extracted from peripheral blood lymphocytes and subjected to direct sequencing of the entire coding region of the AVP-NPII gene. RESULTS AND CONCLUSIONS: Clinical assessment of the patient confirmed the diagnosis of neurohypophyseal diabetes insipidus. Desmopressin treatment was started, which effectively reversed the polyuria/ polydipsia syndrome. Genetic analysis revealed a novel mutation (1665T>A) in exon 2 of the AVP-NPII gene, disrupting one of the disulfide bonds present in the NPII moiety which play a fundamental role in determining the proper folding of the molecule. In summary, in the present study we have described a novel mutation of the AVP-NPII gene, which is consistent with the malfolding/toxicity hypothesis underlying the pathogenesis of adFNDI.

Adult↗
PubMed1984

Cooperative interactions in neurophysin-neuropeptide hormone complexes. Analytical affinity chromatography of native and covalently-modified neurophysins.

The structural interdependence between neurophysin (NP) self-association and ligand binding surfaces has been studied by analytical affinity chromatography of several NP sequence variants and derivatives on Met-Tyr-Phe-aminobutyl-agarose and bovine NP-II Sepharose. Elutions of radiolabeled NP's from both matrices show that hybrid dimers can form between major bovine NP's (I and II, or VLDV- and MSEL-NP's, respectively), as well as between human and bovine NP's, with affinities close to that for homologous dimer formation. Such evidence supports the view that the region of NP involved in NP-NP contact is composed primarily of conserved structural elements of the protein. NP antibodies which recognize surfaces close to or in the NP-NP contact region have been detected by their effects on bovine NP-II elution on NP-II Sepharose. Elutions of [3-nitro-Tyr 49] BNP-II from Met-Tyr-Phe-aminobutyl-agarose showed that nitration has little effect on the chromatographic properties of NP-II. This evidence substantiates previous arguments (Angal, S. & Chaiken, I.M. (1982) Biochemistry 21, 1574-1580) that the chromatographic behavior of native NP's on the affinity matrices is an expression of the interdependence of NP self-association and ligand binding surfaces and not due to bivalent peptide binding by NP monomer. The affinity chromatographic properties of NP derivatives, including bovine NP-II photolabeled in the ligand binding site and tryptic fragments of bovine NP-I (NP-I-(9-93) and [des 19-20] NP-I-(9-93)), support the view that the surfaces for ligand binding and NP-NP contact are conformationally linked. The data argue that conformational changes that ensue upon noncovalent ligand binding and lead to enhanced NP self-association cannot occur favorably with the protein modified by either covalent ligand attachment or limited amino-terminal proteolysis.

Animals↗