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)

In situ hybridization was used to study the mRNA levels for vasopressin, galanin, secretogranin II and carboxypeptidase H in salt-loaded and Brattleboro rats. These animals represent an in vivo model for the chronic stimulation of the hypothalamo-neurohypophyseal neurons. As shown by immunelectron microscopy secretogranin II is co-stored with vasopressin in these neurons. In salt-loaded rats the levels of mRNA for vasopressin, galanin and secretogranin II are increased in the paraventricular and supraoptic nuclei. Analogous changes were observed for Brattleboro rats with the exception of the vasopressin message which was decreased in these animals. The secretogranin II message was also increased in neurons which do not contain the vasopressin mRNA, i.e. in magnocellular neurons of the lateral hypothalamus and in the subfornical organ. Carboxypeptidase H message was also found in the paraventricular and supraoptic nuclei and in the subfornical organ; however, in both models the changes in mRNA in these nuclei were much lower than those observed for the secretory peptides or non-existent. We conclude that chronic stimulation of vasopressin neurons leads to a concomitant up-regulation of the biosynthesis of neuropeptides and secretogranin II. We suggest that the secretogranin II message might be a useful general marker for identifying chronically stimulated neurons.
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PMID:In situ hybridization: mRNA levels of secretogranin II, neuropeptides and carboxypeptidase H in brains of salt-loaded and Brattleboro rats. 137 56

Carboxypeptidase H (CPH) is a peptide-processing enzyme thought to be involved in the synthesis of many neuropeptides, including vasopressin (VP) and oxytocin (OT). In this study, employing in situ hybridization histochemistry, we have shown that CPH mRNA is abundantly expressed in the magnocellular paraventricular and supraoptic nuclei of the hypothalamus, the primary sites of OT and VP synthesis. Since this enzyme is copackaged in secretory vesicles and hence coreleased with the neurohypophysial hormones, enzyme stores are depleted in parallel with the peptide hormones during states of hypersecretion. Chronic osmotic stimulation, such as occurs in long-term salt-loading or in diabetes insipidus in the Brattleboro rat, causes depletion of neurohypophysial hormone stores and is accompanied by increased rates of neurohypophysial hormone transcription and translation. This study has shown that the expression of CPH mRNA is also significantly increased in oxytocin and vasopressin producing magnocellular neurons during chronic osmotic stimulation of the hypothalamic-neurohypophysial system. CPH mRNA levels in other peptidergic areas of the brain are not significantly changed by osmotic stimulation. These findings illustrate a coordinate regulation of the transcription of peptide hormones and an enzyme required for the hormones' posttranslational processing.
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PMID:Regulation of carboxypeptidase H gene expression in magnocellular neurons: response to osmotic stimulation. 262 43

Carboxypeptidase H is one of several enzymes required for the processing of peptide hormone precursors. In this study, inhibition of carboxypeptidase H by its peptide products was investigated. Carboxypeptidase H activity in bovine adrenal medulla chromaffin granules and rat adrenal medulla homogenate was inhibited by the peptides Met- and Leu-enkephalin, vasopressin, oxytocin, luteinizing hormone-releasing hormone, substance P, and thyrotropin-releasing hormone, with oxytocin and ACTH 1-14 having the least effect, at concentrations of 2-20 mM. Inhibition by amidated peptide products (vasopressin, oxytocin, luteinizing hormone-releasing hormone, substance P, and thyrotropin-releasing hormone) show that the final products of the precursor processing pathway can regulate carboxypeptidase H. These levels of peptides are similar to known intragranular peptide concentrations indicating that product and feedback inhibition of carboxypeptidase H may play a role in the control of neuropeptide synthesis. The proenkephalin-derived peptides Met-enkephalin, Leu-enkephalin, Met-enkephalin-Arg6-Gly7-Leu8, and Met-enkephalin-Arg6-Phe7 competitively inhibited bovine and rat carboxypeptidase H with Ki values of 12.0, 6.5, 7.0, and 5.5 mM, respectively. The significantly greater Ki for Met-enkephalin may reflect the effects of higher intragranular concentration of Met-enkephalin, since one proenkephalin molecule contains four copies of Met-enkephalin and only one copy of each of the other enkephalin peptides. Thus, the products from one multivalent precursor molecule may equivalently inhibit carboxypeptidase H activity. Product inhibition of carboxypeptidase H and perhaps other processing enzymes may serve to limit the maximum peptide concentration within the secretory vesicle.
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PMID:Product inhibition of carboxypeptidase H. 288 69

Neuroendocrine peptides play important roles as intercellular messengers. We previously developed a technique to isolate and identify a large number of neuroendocrine peptides from Cpe(fat)/Cpe(fat) mice (Che, F.; et al. Proc. Natl. Acad. Sci. U.S.A. 2001, 98, 9971-6); these mice lack carboxypeptidase E activity and this defect causes an accumulation of neuropeptide intermediates that contain C-terminal Lys or Arg residues (Naggert, J. K.; et al. Nat. Genet. 1995, 10, 135-42). In the present study, we have developed a differential isotopic-labeling technique that can be used to quantitate changes in neuropeptide levels in Cpe(fat)/Cpe(fat) mouse tissues. Samples are treated with either the H6 or the D6 form of acetic anhydride, peptides that contain C-terminal basic amino acids are isolated by affinity chromatography on anhydrotrypsin agarose, and the isolated peptides are analyzed by mass spectrometry. Measurement of the regulation of pituitary peptides in response to dehydration showed a decrease in vasopressin. The general method described in this report should be widely applicable to a large number of neuroendocrine peptides, known and novel, in a variety of regulatory paradigms.
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PMID:Quantitation of neuropeptides in Cpe(fat)/Cpe(fat) mice using differential isotopic tags and mass spectrometry. 1214 82