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)

Systematic analysis of the hydrolysis of benzyloxycarbonyl (Cbz)-dipeptides by cathepsin A [EC 3.4.12.1] purified from rat liver lysosomes showed that multiple forms of cathepsin A preferentially cleave peptide bonds with leucine, methionine, and phenylalanine. Cbz-Met-Met, -Met-Phe, -Phe-Met, and -Phe-Ala were hydrolyzed 6 to 8 times faster than the standard substrates, Cbz-Glu-Phe and Cbz-Glu-Tyr. The pH optima of the hydrolyses were 4.6 to 5.8. Hydrolysis of peptide bonds with glycine, isoleucine, and proline was very slow, but the rate depended on the nature of the adjacent amino acids. Proteins such as albumin, cytochrome c, gamma-globulin, hemoglobin, histone, myoglobin, and myosin were scarecely degraded. Peptide hormones, such as glucagon and adrenocorticotropic hormone (ACTH) were hydrolyzed markedly with optimum pH's of 4.5 and 4.6, respectively. Angiotensin I, II, bradykinin, Lys- and Met-Lysbradykinin (kallidin and Met-kallidin), and substance P were also hydrolyzed at appreciable rates. pH optima for these peptide hormones were 5.2 to 5.6. On the other hand, insulin and its A chain, luteinizing hormone-releasing hormone (LH-RH), oxytocin and vasopressin were cleaved slowly. In the hydrolyses of glucagon and other peptides, multiple forms of rat liver lysosomal cathepsin A again showed a carboxypeptidase nature, cleaving peptide bonds sequentially from the carboxyl terminal. Almost all of the amino acids were cleaved on prolonged incubation. Vaso-activites of angiotensin II and bradykinin were rapidly lost on hydrolysis by cathepsin A. Lysosomal cathepsin C [dipeptidylaminopeptidase I, EC 3.4.14.1] also activated angiotensin II, but did not inactive bradykinin. Cathepsin A, therefore, can be regarded as one of the lysosomal angiotensinases and kinases. No distinct differences were observed between the multiple forms of cathepsin A in these hydrolyses and inactivations of peptides.
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PMID:Studies on cathepsins of rat liver lysosomes. III. Hydrolysis of peptides, and inactivation of angiotensin and bradykinin by cathepsin A. 1 61

1. The effects on phosphatidylinositol metabolism of three Ca(2+)-mobilizing glycogenolytic hormones, namely angiotensin, vasopressin and adrenaline, have been investigated by using rat hepatocytes. 2. All three hormones stimulate both phosphatidylinositol breakdown and the labelling of this lipid with (32)P. 3. The response to angiotensin occurs quickly, requires a high concentration of the hormone and is prevented by [1-sarcosine, 8-isoleucine]angiotensin, a specific angiotensin antagonist that does not prevent the responses to vasopressin and to adrenaline. This response therefore seems to be mediated by angiotensin-specific receptors. 4. [1-Deaminocysteine,2-phenylalanine,7-(3,4-didehydroproline),8-arginine] vasopressin, a vasopressin analogue with enhanced antidiuretic potency, is relatively ineffective at stimulating phosphatidylinositol metabolism. This suggests that the hepatic vasopressin receptors that stimulate phosphatidylinositol breakdown are different in their ligand selectivity from the antidiuretic vasopressin receptors that activate renal adenylate cyclase. 5. Incubation of hepatocytes with ionophore A23187, a bivalent-cation ionophore, neither mimicked nor appreciably changed the effects of vasopressin on phosphatidylinositol metabolism, suggesting that phosphatidylinositol breakdown is not controlled by changes in the cytosol Ca(2+) concentration. This conclusion was supported by the observation that hormonal stimulation of phosphatidylinositol breakdown and resynthesis persists in cells incubated for a substantial period in EGTA, although this treatment somewhat decreased the phosphatidylinositol response of the hepatocyte. The phosphatidylinositol response of the hepatocyte therefore appears not to be controlled by changes in cytosol [Ca(2+)], despite the fact that this ion is thought to be the second messenger by which the same hormones control glycogenolysis. 6. These results may be an indication that phosphatidylinositol breakdown is an integral reaction in the stimulus-response coupling sequence(s) that link(s) activation of alpha-adrenergic, vasopressin and angiotensin receptors to mobilization of Ca(2+) in the rat hepatocyte.
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PMID:Phosphatidylinositol metabolism in rat hepatocytes stimulated by glycogenolytic hormones. Effects of angiotensin, vasopressin, adrenaline, ionophore A23187 and calcium-ion deprivation. 22 24

Preliminary studies determined that, unlike other purported alpha-2 adrenoceptor agonists, 2,6-dimethyl clonidine (2,6-DMC) increased urine flow rate independent of vasopressin. We therefore compared the dose-response curves of three alpha-2 adrenoceptor agonists, clonidine, UK 14,304 and 2,6-DMC. Unilaterally nephrectomized Sprague-Dawley rats were anesthetized and the left kidney was exposed and the ureter cannulated. A 31-gauge needle was advanced into the renal artery to permit direct intrarenal infusion of the study drugs. All three agonists produced a dose-related increase in urine flow rate and sodium excretion. A clear opposite rank order of potency was observed when the urine flow rate was analyzed as free water and osmolar clearance. For free water clearance, clonidine much greater than UK 14,304 much greater than 2,6-DMC, with 2,6-DMC producing little change. The effect on osmolar clearance was opposite with 2,6-DMC much greater than clonidine = UK 14,304. The V2 antagonist [1-(beta-mercapto-beta,beta-pentamethylene-proprionic acid), 2-d-isoleucine,4-isoleucine]arginine-vasopressin blocked the effects of clonidine but not 2,6-DMC. In a water-loaded rat model, 2,6-DMC but not clonidine increased the delivery of filtrate out of the proximal segments of the nephron. These results are consistent with the postulate that lower doses of 2,6-DMC increase solute excretion independent of vasopressin, possibly in proximal segments of the nephron. Clonidine on the other hand increases free water clearance and this effect is mediated through an interaction with the renal actions of vasopressin. Whether these disparate effects represent two distinct receptors or two sites of alpha-2 adrenoceptors in the kidney is not known.
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PMID:Opposite rank order of potency for alpha-2 adrenoceptor agonists on water and solute excretion in the rat: two sites and/or receptors? 135 Oct 96

Indirect immunofluorescence histochemistry was used to investigate the distribution and extent of co-localization of chemical messengers in magnocellular neurons of the supraoptic and paraventricular nuclei. In order to increase the number of neurons immunoreactive to the antisera used, experimental manipulations were employed. The homozygous Brattleboro (diabetes insipidus) rat was also investigated. In untreated rats, only vasopressin- and oxytocin-like immunoreactivities could be observed. Colchicine treatment alone resulted in appearance of galanin-, dynorphin-, cholecystokinin-, [Leu]enkephalin- and thyrotropin-releasing hormone-positive cells. In hypophysectomized rats, all these markers, except tyrosine hydroxylase, showed substantial further increases. In addition, peptide histidine-isoleucine-immunoreactive cell bodies could now be seen. After salt-loading alone, tyrosine hydroxylase-like immunoreactivity was markedly increased, whereas vasopressin- and oxytocin-like immunoreactivity were very weak or undetectable. When salt-loaded rats received colchicine, corticotropin-releasing factor- and peptide histidine-isoleucine-like immunoreactivity in addition increased, whereas galanin- and dynorphin-like immunoreactivity markedly decreased. The Brattleboro rats resembled untreated rats, except their lack of vasopressin-like immunoreactivity, the marked increase in tyrosine hydroxylase-like immunoreactivity, and smaller increase in galanin- and dynorphin-like immunoreactivity. Addition of colchicine to Brattleboro rats resulted in some distinct further changes in that dynorphin-like immunoreactivity decreased in some neurons and that [Leu]enkephalin-, corticotropin-releasing factor- and peptide histidine-isoleucine-like immunoreactivity increased substantially. Several similarities could be observed between the salt-loaded and Brattleboro rats, with or without colchicine. However, a marked difference in immunoreactive [Leu]enkephalin levels was observed with no difference in dynorphin-like immunoreactivity, and opposite changes in galanin-like immunoreactivity. The results confirm the traditional view that hypothalamic magnocellular neurons in the supraoptic and paraventricular nuclei contain two separate cell populations, characterized by vasopressin and oxytocin, respectively, and that they contain additional messenger molecules in specific patterns. Vasopressin-containing neurons primarily express tyrosine hydroxylase, galanin, dynorphin, [Leu]enkephalin and peptide histidine-isoleucine, and to a minor extent cholecystokinin and thyrotropin-releasing hormone. Oxytocin-containing neurons mainly have cholecystokinin and corticotropin-releasing factor, and to a minor extent galanin, dynorphin, [Leu]enkephalin and thyrotropin-releasing hormone. Furthermore, our results detail individual co-existence situations among these putative messenger molecules. Thus, magnocellular neurons respond in a differential way to various stimuli and they store multiple bioactive substances in specific combinations.
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PMID:Localization of chemical messengers in magnocellular neurons of the hypothalamic supraoptic and paraventricular nuclei: an immunohistochemical study using experimental manipulations. 170 Oct 38

Rat thoracic aortic smooth muscle cells (line A10, ATCC CRL 1476) display a high density of atrial natriuretic factor (ANF) receptors. ANF stimulated the accumulation of cGMP in these cells in a time- and dose-dependent fashion. These cells are known to display a high density of vasopressin receptors of the vascular V1 subtype. These vasopressin receptors mediate inhibition of isoproterenol-stimulated cAMP accumulation and stimulation of inositol phosphate accumulation and calcium fluxes. Addition of [8-arginine]vasopressin ([Arg8]VP) to these cells inhibited ANF-stimulated cGMP accumulation. Inhibition of cGMP accumulation was dependent on the concentration of [Arg8]VP, with half-maximal and maximal effects occurring at 0.4 and 10 nM, respectively. [Arg8]VP did not have significant effects on basal cGMP levels. The inhibition by [Arg8]VP appears to be mediated by V1 receptors, since the V2 renal receptor agonist [1-desaminocysteine,8-D-arginine]vasopressin was ineffective. Also, the selective V1 antagonist [1-(beta-mercapto-beta,beta-cyclopentamethylenepropionic acid),2-(O-methyltyrosine),8-arginine]vasopressin and the mixed V1/V2 antagonist [1-(beta-mercapto-beta,beta-cyclopentamethylenepropionic acid),2-(O-ethyl-D-tyrosine),4-valine,8-arginine]vasopressin blocked the [Arg8]VP-mediated effect, whereas the selective V2 antagonist [1-(beta-mercapto-beta,beta-cyclopentamethylenepropionic acid), 2-D-isoleucine,4-valine,8-arginine]vasopressin was minimally effective. These data show that in rat aortic smooth muscle cells, V1 receptors are negatively coupled to guanylate cyclase. These data also suggest that the vasoconstrictor activity of [Arg8]VP might involve inhibition of ANF-receptor-mediated vascular relaxation through inhibition of cGMP accumulation in addition to its effects on isoproterenol-mediated cAMP accumulation and inositol phosphate accumulation and calcium fluxes.
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PMID:Vasopressin-mediated inhibition of atrial natriuretic factor-stimulated cGMP accumulation in an established smooth muscle cell line. 243 Feb 90

The occurrence and distribution of peptide-containing nerve fibers to the cerebral circulation are described. Immunocytochemical studies have revealed that cerebral blood vessels are invested with nerve fibers containing neuropeptide Y (NPY), vasoactive intestinal peptide (VIP), peptide histidine isoleucine (PHI), substance P (SP), neurokinin A (NKA), and calcitonin gene-related peptide (CGRP). In addition, there are studies reporting the occurrence of putative neurotransmitters such as cholecystokinin, dynorphin B, galanin, gastrin releasing peptide, vasopressin, neurotensin, and somatostatin. The nerves occur as a longitudinally oriented network around large cerebral arteries. There is often a richer supply of nerve fibers around arteries than veins. The origin of these nerve fibers has been studied by retrograde tracing and denervation experiments. These techniques, in combination with immunocytochemistry, have revealed a rather extensive innervation pattern. Several ganglia, such as the superior cervical ganglion, the sphenopalatine ganglion, the otic ganglion, and small local ganglia at the base of the skull, contribute to the innervation. Sensory fibers seem to derive from the trigeminal ganglion, the jugular-nodose ganglionic complex, and from dorsal root ganglia at level C2. The noradrenergic and most of the NPY fibers derive from the superior cervical ganglion. A minor population of the NPY-containing fibers contains VIP instead of NA and emanates from the sphenopalatine ganglion. The cholinergic and the VIP-containing fibers derive from the sphenopalatine ganglion, the otic ganglion, and from small local ganglia at the base of the skull. Most of the SP-, NKA-, and CGRP-containing fibers derive from the trigeminal ganglion. Minor contributions may emanate from the jugular-nodose ganglionic complex and from the spinal dorsal root ganglia. NPY is a potent vasoconstrictor in vitro and in situ. VIP, PHI, SP, NKA, and CGRP act via different mechanisms to induce cerebrovascular dilatation. The sympathetic, the parasympathetic, and the sensory systems appear to be involved in modulating cerebrovascular tone in hypertension and in conditions of threatening vasoconstriction, e.g., subarachnoid hemorrhage and migraine.
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PMID:Neuropeptides in the cerebral circulation. 270 77

[4-(0-methyl)-L-threonine]-oxytocin, a new analogue of neurohypophyseal hormone oxytocin, was synthesized. Its uretonic activity was found to be 150 I. U./mg. The comparison of the potency of [4-(0-methyl)-threonine]-oxytocin with a very active analogue [4-threonine]-oxytocin and low active analogue [4-isoleucine] -oxytocin supports the hypothesis of high uterotonic activity of 4-substituted analogue of oxytocin to be related to the presence of suitably located hydrophilic and lipophilic grouper in the side chain in position 4, and to the proton donor/proton acceptor properties of hydrophilic group.
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PMID:[4-(0-methyl)-L-threonine] -oxytocin. Synthesis and uterotonic activity. 285 67

Messenger RNAs (mRNA) coding for vasoactive intestinal polypeptide (VIP), peptide histidine isoleucine (PHI), somatostatin and vasopressin were localized in the suprachiasmatic nucleus (SCN) of the rat hypothalamus using in situ hybridization histochemistry. Specific mRNA coding for each of these peptides was distributed in areas coextensive with the immunohistochemical localization of the appropriate peptide. The autoradiographic signal produced with probes to VIP and PHI created dense concentrations of silver grains over neuronal perikarya in the ventrolateral SCN, and the coextensive distribution of both VIP- and PHI-mRNAs suggests that both peptides are synthesized within the same neurons. The distribution of somatostatin-mRNA was distinct from the of VIP and PHI. Labeled neurons are observed at the interface of the two SCN subdivisions and the distribution of these neurons is identical to those shown to contain somatostatin immunoreactivity. Vasopressin-mRNA is also differentially concentrated within neurons in the dorsomedial subdivision of the SCN in an area that is coextensive with vasopressin-immunoreactive perikarya. The discrete pattern of hybridization for each of these mRNAs indicates that each of these peptides are synthesized in SCN neurons and reaffirms the differential distribution of each of these chemically defined cell populations within cytoarchitecturally distinct subdivisions of the nucleus.
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PMID:Localization of vasopressin-, vasoactive intestinal polypeptide-, peptide histidine isoleucine- and somatostatin-mRNA in rat suprachiasmatic nucleus. 289 92

Analysis of peptides purified from high and low molecular weight fractions of rabbit atrial extracts indicates that the sequence of the first 30 residues of rabbit atriopeptigen exhibits 80% homology with the rat peptide, and that the low molecular weight rabbit peptide (28 residues) is identical to rat atriopeptin 28 (AP 28). The effects of infused 1-deaminoarginine8-vasopressin (dAVP) and phenylephrine, volume expansion, and water immersion on AP release into the circulation of the rabbit was studied. Neither dAVP, nor water immersion elevated right atrial pressure (RAP) or plasma AP levels in the anesthetized rabbits. Phenylephrine induced a sustained increase in systemic blood pressure and right atrial pressure which was accompanied by elevated plasma AP immunoreactivity which appeared to be identical to rat AP-28 on HPLC. There is obviously a preferential conservation of the AP sequence, since the C-terminal peptide is exactly the same in rabbit, rat and mouse and differs from human, dog, cow and pig only by the single substitution of an isoleucine for a methionine residue.
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PMID:Identification of the cardiac and circulating form of atriopeptin in rabbit. 294 16

Arginine vasopressin (AVP), a nine-amino acid neurohypophyseal hormone, is capable of replacing the helper cell requirement for IFN-gamma production by Lyt-2+ mouse splenic lymphocytes. We present data here showing that the AVP helper signal occurs via interaction with a novel R on splenic lymphocytes and involves primarily the N-terminal six-amino acid cyclic ring (pressinoic acid) with the C-terminal three-amino acid end of AVP playing a minor role. Pressinoic acid was capable of providing help at concentrations similar to those of AVP, whereas oxytocin and isoleucine pressinoic acid were 10- and 100-fold less effective, respectively. Isoleucine pressinoic acid has the same structure as pressinoic acid except for the substitution of isoleucine for phenylalanine in position 3 of the sequence. Consistent with the function data, R binding competitions with splenic lymphocyte membrane preparations showed that AVP and pressinoic acid competed similarly with [3H]AVP, whereas oxytocin and isoleucine pressinoic acid were much less effective competitors. Further characterization of the AVP lymphocyte R was performed using AVP analogues having well defined agonist and antagonist activities on either V1 (vasopressor) R or V2 (antidiuretic) R. The AVP helper signal was blocked by the V1 antagonist [d(CH2)1(5) Tyr(methyl)]AVP but not by another V1 antagonist, [d(CH2)1(5)D-Tyr(ethyl)2Val4]AVP. Both V1-R antagonists were able to block [3H]AVP binding to the V1-R on liver cells, whereas only the V1 antagonist that blocked AVP help was able to compete effectively for the spleen AVP-R. Neither a V2 agonist nor a V2 antagonist had any effect on AVP help in IFN-gamma production. These data strongly indicate the presence of a novel AVP-R on spleen lymphocytes, which is related to the classic V1-R on liver cell membranes.
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PMID:Arginine vasopressin (AVP) replacement of helper cell requirement in IFN-gamma production. Evidence for a novel AVP receptor on mouse lymphocytes. 296 81


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