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)

Two genes each encoding a distinct precursor protein to the hormone isotocin and a neurophysin-related protein are present in the teleost fish Catostomus commersoni. These precursors are referred to as isotocin 1 and 2. As shown by the polymerase chain reaction technique, both genes lack introns in their protein-coding sequences. Both genes are transcribed giving rise to mRNAs of 920 (isotocin 1) and 1020 (isotocin 2) bases, respectively. Based on the nucleotide sequences, the predicted isotocin precursors contain, besides the hormone moiety, a neurophysin-like protein that, in contrast to its mammalian counterpart, is extended at its C-terminus by a peptide which includes a leucine-rich core segment. This segment shows similarities to the copeptin of the mammalian vasopressin precursor that is known to possess prolactin-releasing activity. The data imply that the mammalian copeptin sequence was initially part of a larger ancestral neurophysin molecule.
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PMID:Two isotocin genes are present in the white sucker Catostomus commersoni both lacking introns in their protein coding regions. 258 84

The nucleotide sequences of cloned cDNAs encoding the precursors for vasotocin and isotocin have been elucidated by analyzing a lambda gt11 library constructed from poly(A)+ RNA from the hypothalamic region of the teleost fish Catostomus commersoni. Screening of the library was carried out with synthetic oligonucleotide probes deduced from the amino acid sequences of the nonapeptides vasotocin and isotocin. The cDNA nucleotide sequences predict isotocin and vasotocin prohormone precursors each consisting of a signal peptide, a hormone moiety, and a neurophysin-like molecule. However, in comparison to their mammalian counterparts, both fish neurophysins are extended at their C termini by an approximately 30 amino acid sequence with a leucine-rich core segment. These extensions show striking similarities with the glycopeptide moiety (the so-called copeptin) present in mammalian vasopressin precursors, except that they lack the consensus sequence for N-glycosylation. These data suggest that mammalian copeptin is derived from the C terminus of an ancestral neurophysin.
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PMID:Vasotocin and isotocin precursors from the white sucker, Catostomus commersoni: cloning and sequence analysis of the cDNAs. 274 82

The lysosomes of hepatocytes increase in numbers and size during acute cell injury in vivo. To elucidate the mechanism of this change, we have studied in vitro the response of the autophagic lysosomal system to several physiologic mediators of autophagy, and to agents known to induce injury and/or the accumulation of lysosomes in vivo. To this end, monolayer cultures of rat hepatocytes were labeled with [14C]leucine to measure hepatocyte protein degradation; ultrastructural analyses were carried out to measure the volume fraction of lysosomes in the hepatocytes. Dibutyryl cyclic AMP increased protein degradation in the hepatocytes either in the presence or absence of serum and insulin. Deprivation of serum and insulin also increased hepatocyte protein degradation. Morphometric analysis indicated parallel increases in the volume fraction of lysosomes in the hepatocytes. The calcium ionophore ionomycin (5 microM), in the presence of 1.3 mM extracellular calcium, increased protein degradation (but not the volume fraction of lysosomes), and this increase was abolished by the addition of ethyleneglycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid. On the other hand, vasopressin (5 nM) caused an increase in protein degradation coupled with an increase in volume fraction of lysosomes. The microtubule depolymerizer vinblastine decreased protein degradation. The microtubule stabilizer taxol did not prevent the inhibitory effects caused by vinblastine. Parallel decreases in the lysosomal compartment were found in the hepatocytes exposed to vinblastine or taxol. Dimethylnitrosamine inhibited protein degradation as well as decreased the volume fraction of lysosomes. Finally, carbon tetrachloride also decreased protein degradation. These data indicate that in physiologic conditions, increases in numbers of hepatocyte lysosomes reflect increased sequestration and degradation of cytoplasmic proteins in response to changes in the levels of hormones, serum factors and nutrients as well as cyclic AMP. The induction of acute cell injury in vitro by calcium ionophore, microtubule active agents, and hepatotoxins inhibits lysosomal proteolysis and causes a decrease in the volume fraction of lysosomes. We conclude that the increase in lysosomal size and numbers occurring in acutely injured hepatocytes in vivo is induced primarily by altered levels of nutritional and hormonal regulators of lysosomal protein degradation.
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PMID:Response of autophagic protein degradation to physiologic and pathologic stimuli in rat hepatocyte monolayer cultures. 283 7

Specific radioimmunoassays were used to measure the effects of hypertonic saline (salt loading), water deprivation, and trichothecene mycotoxin (T2 toxin) on the content of methionine enkephalin (ME), leucine enkephalin (LE), alpha-neoendorphin, dynorphin A, dynorphin B, vasopressin, and oxytocin in the rat posterior pituitary. Concentrations of vasopressin and oxytocin decreased in response to both osmotic stimuli and treatment with T2 toxin, but the decrease was greater with osmotic stimulations. Similarly, concentrations of LE and dynorphin-related peptides declined after salt loading and water deprivation; LE concentrations also decreased after treatment with T2 toxin. The concentration of ME decreased after water deprivation, did not change after salt loading, and increased after T2 toxin treatment. The differentiating effects of these stimuli on the content of immunoreactive LE and ME are consistent with the hypothesis that LE and ME may be localized in separate populations of nerve endings with different roles in the posterior pituitary.
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PMID:Methionine and leucine enkephalin in rat neurohypophysis: different responses to osmotic stimuli and T2 toxin. 285 18

The incorporation of leucine into protein was studied in Ca2+-depleted and Ca2+-restored preparations of normal liver cells isolated from fed, adult male rats. Ca2+-restored cells incorporated amino acid 5-10-fold more rapidly than did Ca2+-depleted cells for incubation periods up to 1 hr. Readdition of Ca2+ at supraphysiologic concentrations (3 mM) to depleted cells restored the rate of incorporation within 8-10 min, whereas lesser concentrations of the cation acted more slowly. Vasopressin and alpha-adrenergic agonists rapidly (in minutes) inhibited amino acid incorporation to variable degrees in liver cells, with pronounced inhibitions (40-75%) occurring at moderate (0.1-1 mM) extracellular Ca2+ concentrations and smaller inhibitions (10-30%) occurring at supraphysiologic concentrations of the cation. Hormonally produced inhibitions were more intense at acid pH than at alkaline pH. The effects of epinephrine were mediated through alpha 1-adrenergic receptors and were not additive with those of vasopressin at saturating concentrations. It is proposed that these hormones, which are known to mobilize sequestered Ca2+ within liver cells, inhibit amino acid incorporation by influencing a Ca2+ requirement associated with protein synthesis.
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PMID:Regulation of protein synthesis in isolated hepatocytes by calcium-mobilizing hormones. 286 10

A new strategy was devised for the targeted immobilization of ligands on aminohexyl- and carboxyhexyl-agarose. Selectively protected neurotransmitter amino acids and neuropeptides were coupled to amino or carboxyl group-containing agarose derivatives using activated esters, mixed anhydrides or carbodiimides. After coupling, agarose beads were dehydrated and the protecting groups were cleaved in non-aqueous media with acids (trifluoroacetic acid, formic acid). Agarose beads were rehydrated and applied for affinity chromatography and cell surface recognition. The same compounds were coupled to derivatized polyacrylamide beads containing primary amino (Acrylex A), acyl hydrazide (Acrylex AH-100) or carboxyl (Acrylex C-100) groups. Protecting groups were removed by acidolytic cleavage. Oxytocin, vasopressin, tetra- and pentagastrin, cholecystokinin, leucine-enkephalin and carboxyl-bearing derivatives of the neurotransmitters noradrenaline, dopamine, histamine, serotonin, acetylcholine and gamma-aminobutyric acid were immunobilized on agarose and on derivatized polyacrylamide gels.
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PMID:Targeted immobilization of neurotransmitters and neuropeptides on agarose and on Acrylex polymers. 287 23

The content of vasopressin, oxytocin, neurophysin, leucine-enkephalin, methionine-enkephalin, dynorphin-(1-13), and alpha-neoendorphin in the rat neurohypophysis was measured after different periods of dehydration and after depolarisation of isolated neural lobes and of neurosecretory nerve endings. The rates at which the amount of neurohypophysial hormone and opioid peptides decreased, and the changes in the ratios between the amount of vasopressin or oxytocin and opioid peptide in the neurohypophysis after dehydration and in the incubation medium after depolarization in vitro cast some doubt on, and can be explained by mechanisms other than co-localisation of the different peptides.
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PMID:Are opioid peptides co-localized with vasopressin or oxytocin in the neural lobe of the rat? 287 38

The anteroventral periventricular nucleus (AVPv), which lies in the periventricular zone of the preoptic region, is critical for normal phasic gonadotropin secretion since lesions of this nucleus abolish the progesterone-induced surge of luteinizing hormone secretion from the anterior pituitary, block ovulation, and induce persistent vaginal estrus in female rats. However, very little is known about the neurotransmitter-specific pathways associated with this nucleus. In the present study we evaluated the distribution of biochemically specific cells and fibers within the AVPv and adjacent regions by using an indirect immunohistochemical method with antisera to serotonin (5-HT), dopamine beta-hydroxylase (DBH), tyrosine hydroxylase (TH), neuropeptide Y (NPY), cholecystokinin-8 (CCK), vasoactive intestinal polypeptide (VIP), substance P (SP), neurotensin (NT), corticotropin-releasing factor (CRF), luteotropin-releasing hormone (LRH), somatostatin (SS), thyrotropin-releasing hormone (TRH), oxytocin (OXY), vasopressin (VAS), adrenocorticotropic hormone (ACTH1-24), alpha-melanocyte-stimulating hormone (alpha-MSH), leucine-enkephalin (L-ENK), and calcitonin gene-related peptide (CGRP). Our findings indicate that both cells and fibers containing these putative neurotransmitters are differentially distributed in and around the AVPv in accordance with the cytoarchitectonic organization of this part of the preoptic region. The AVPv itself appears to receive strong inputs from SP-, VAS-, CCK-, and SS-containing pathways, whereas the highest densities of L-ENK-, NT-, 5-HT-, NPY-, and DBH-immunoreactive fibers were found in the cell-sparse zone just lateral to the AVPv. The suprachiasmatic preoptic nucleus (PSCh), a small group of cells located ventral to the AVPv just dorsal to the optic chiasm, contained high densities of alpha-MSH- and ACTH-immunoreactive fibers, as well as substantial numbers of fibers containing catecholamines or NPY. In contrast, a dense plexus of VAS-stained fibers was distributed fairly evenly throughout the AVPv and PSCh. Numerous L-ENK-immunoreactive cell bodies, and moderate numbers of CCK-, NT-, and CRF-stained cell bodies were found in the AVPv. The PSCh contained many TH-stained cells (presumably dopaminergic), in addition to a moderate number of CCK-containing cell bodies, while a high density of NT- and CRF-stained cells were found in the cell-sparse zone lateral to the AVPv, in addition to several CCK-, SP-, VIP-, and TH-containing cells.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The distribution of neurotransmitter-specific cells and fibers in the anteroventral periventricular nucleus: implications for the control of gonadotropin secretion in the rat. 288 Jun 34

We addressed in this study, with immunocytochemical methods, the following questions: are immunoreactive enkephalins in the rat neurohypophysis stored in nerves distinct from neurosecretory nerves; where is [Met]enkephalin immunoreaction localized; does immunoreactive [Leu]enkephalin coexist with pro-enkephalin or with pro-dynorphin fragments; and are the interpretations of localization studies influenced by the choice of pre-embedding or post-embedding immunocytochemical techniques? We compared immunoreactions due to antibodies which had been used by others in previous studies, examined both lyophilized and conventionally fixed specimens, and applied pre- and post-embedding protocols. Both pre- and post-embedding stainings confirmed co-storage of immunoreactive dynorphin(1-8)-like materials with vasopressin. Immunoreactive [Met]enkephalin-like material always coexisted with oxytocin. Most of the immunoreactive [Leu]enkephalin-like material appeared to occur in oxytocin nerves; only in larger vasopressin varicosities was there some dot-like [Leu]enkephalin immunoreaction. This indicates that neural lobe [Leu]enkephalin predominantly is cleaved from a precursor which also contains [Met]enkephalin. When pre-embedding methods were modified in order to block diffusion and to enhance penetration of antibodies, enkephalin immunoreactivity was always found in typical neurosecretory varicosities with large granules. Structures previously interpreted as enkephalinergic nerve terminals contacting pituicytes most likely are neurosecretory varicosities.
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PMID:A re-examination of the localization of immunoreactive dynorphin(1-8), [Leu]enkephalin and [Met]enkephalin in the rat neurohypophysis. 288 79

We describe the synthesis and some pharmacological properties of 16 new in vivo antagonists of oxytocin. These are based on modifications of three peptides: A, B, and C. A is our previously reported potent and selective antagonist of the vasopressor (V1 receptor) responses to arginine-vasopressin (AVP)/weak oxytocin antagonist, [1-(beta-mercapto-beta,beta-pentamethylenepropionic acid), 2-O-methyltyrosine]arginine-vasopressin (d(CH2)5[Tyr(Me)2]AVP. B reported here, the Ile3 analogue of A, is d(CH2)5[Tyr(Me)2]AVT (5 below) and C is our previously reported potent nonselective oxytocin antagonist/AVP V1 antagonist, [1-(beta-mercapto-beta,beta-pentamethylenepropionic acid),2-O- methyltyrosine,8-ornithine]vasotocin (d(CH2)5[Tyr(Me)2]OVT). The following substitutions and deletions, alone or in combination, were employed in A, B, and C: 1-deaminopenicillamine (dP); D-Tyr(Alk)2 (where Alk = Me or Et), D-Phe2; Val4, Thr4; delta 3-Pro7; Lys8, Cit8; desGly9, desGly-NH2(9), Ala-NH2(9); Leu-NH2(9); Arg-NH2(9). The 16 new analogues are (1) d(CH2)5[D-Tyr(Me)2]AVP, (2) d(CH2)5[D-Tyr(Me)2, Val4,delta 3-Pro7]AVP, (3) d(CH2)5[D-Tyr-(Et)2, Val4,Lys8]VP, (4) d(CH2)5[D-Tyr(Et)2,Val4,Cit8]VP, (5) d(CH2)5[Tyr(Me)2]AVT, (6) d(CH2)5[Tyr(Me)2,Lys8]VT, (7) dP[Tyr(Me)2]AVT, (8) dP[Tyr(Me)2,Val4]AVT, (9) d(CH2)5[D-Tyr(Me)2, Val4]AVT, (10) d(CH2)5[D-Phe2,Val4]AVT, (11) d(CH2)5[Tyr(Me)2,Thr4]OVT, (12) d(CH2)5[Tyr(Me)2,Thr4,Ala-NH2(9)]OVT, (13) d(CH2)5[Tyr(Me)2,Thr4,Leu-NH2(9)]OVT, (14) d(CH2)5[Tyr(Me)2,Thr4,Arg-NH2(9)]OVT, (15) desGly-NH2(9),d(CH2)5[Tyr(Me)2,Thr4]OVT, (16) desGly9,d(CH2)5[Tyr(Me)2,Thr4]OVT. 1-4 are analogues of A, 5-10 are analogues of B, and 11-16 are analogues of C. Their protected precursors were synthesized either entirely by the solid-phase method or by a combination of solid-phase and solution methods (1 + 8 or 8 + 1 couplings). All analogues were tested in rats for agonistic and antagonistic activities in oxytocic (in vitro, without and with Mg2+, and in vivo) assays as well as by antidiuretic and vasopressor assays. All analogues exhibit potent oxytocic antagonism in vitro and in vivo. With an in vitro pA2 (in the absence of Mg2+) = 9.12 +/- 0.09, dP[Tyr(Me)2]AVT is (7) one of the most potent in vitro oxytocin antagonists reported to date. Fifteen of these analogues (all but 6) appear as potent or more potent in vivo oxytocin antagonists than C (pA2 = 7.37 +/- 0.17). Analogues 1-9 and 14 are potent AVP V1 antagonists. Their anti-V1 pA2 values range from 7.92 to 8.45. They are thus nonselective oxytocin antagonists.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Solid-phase synthesis of 16 potent (selective and nonselective) in vivo antagonists of oxytocin. 291 98


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