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Evaluation of the degradation of desamino1,D-arginine8-vasopressin by nasal mucosa.

Jönsson, Karin ; Alfredsson, Karin ; söderberg-ahlm, Christina ; Critchley, Helen ; Broeders, Anja and Ohlin, Mats LU orcid (1992) In Acta Endocrinologica 127(1). p.27-32
Abstract
The nasal route is a convenient and simple way to administer peptides to humans. Absorption of the drug, however, requires passage of the substance through the nasal mucosa. This is a possible site of enzymatic degradation of the peptide. It is shown that rabbit nasal mucosa homogenates rapidly degrade the synthetic anti-diuretic hormone analogue desamino1,D-arginine8-vasopressin in vitro. The metabolite formed has been identified as des-(amino,arginine8,glycineamide9)-vasopressin, which is stable under the prevalent in vitro incubation conditions. It is proposed that this process is catalyzed by intracellular post-proline cleavage enzyme. Reversed phase chromatography in combination with immunological detection has been used to study the... (More)
The nasal route is a convenient and simple way to administer peptides to humans. Absorption of the drug, however, requires passage of the substance through the nasal mucosa. This is a possible site of enzymatic degradation of the peptide. It is shown that rabbit nasal mucosa homogenates rapidly degrade the synthetic anti-diuretic hormone analogue desamino1,D-arginine8-vasopressin in vitro. The metabolite formed has been identified as des-(amino,arginine8,glycineamide9)-vasopressin, which is stable under the prevalent in vitro incubation conditions. It is proposed that this process is catalyzed by intracellular post-proline cleavage enzyme. Reversed phase chromatography in combination with immunological detection has been used to study the possible presence of this metabolite in the circulation after intranasal administration to humans. The metabolite des-(amino,arginine8,glycineamide9)-vasopressin could not be detected in plasma following intranasal administration, possibly indicating a paracellular absorption of desamino1,D-arginine8-vasopressin or absence of this enzymatic activity in humans. (Less)
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author
; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Acta Endocrinologica
volume
127
issue
1
pages
27 - 32
publisher
Society of the European Journal of Endocrinology
external identifiers
  • scopus:0026739882
ISSN
0001-5598
DOI
10.1530/acta.0.1270027
language
English
LU publication?
yes
id
b7b0d43d-c17f-4b6f-a7d6-e83b6499a4e2
date added to LUP
2022-12-05 14:40:07
date last changed
2023-05-26 04:04:17
@article{b7b0d43d-c17f-4b6f-a7d6-e83b6499a4e2,
  abstract     = {{The nasal route is a convenient and simple way to administer peptides to humans. Absorption of the drug, however, requires passage of the substance through the nasal mucosa. This is a possible site of enzymatic degradation of the peptide. It is shown that rabbit nasal mucosa homogenates rapidly degrade the synthetic anti-diuretic hormone analogue desamino1,D-arginine8-vasopressin in vitro. The metabolite formed has been identified as des-(amino,arginine8,glycineamide9)-vasopressin, which is stable under the prevalent in vitro incubation conditions. It is proposed that this process is catalyzed by intracellular post-proline cleavage enzyme. Reversed phase chromatography in combination with immunological detection has been used to study the possible presence of this metabolite in the circulation after intranasal administration to humans. The metabolite des-(amino,arginine8,glycineamide9)-vasopressin could not be detected in plasma following intranasal administration, possibly indicating a paracellular absorption of desamino1,D-arginine8-vasopressin or absence of this enzymatic activity in humans.}},
  author       = {{Jönsson, Karin and Alfredsson, Karin and söderberg-ahlm, Christina and Critchley, Helen and Broeders, Anja and Ohlin, Mats}},
  issn         = {{0001-5598}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{27--32}},
  publisher    = {{Society of the European Journal of Endocrinology}},
  series       = {{Acta Endocrinologica}},
  title        = {{Evaluation of the degradation of desamino1,D-arginine8-vasopressin by nasal mucosa.}},
  url          = {{http://dx.doi.org/10.1530/acta.0.1270027}},
  doi          = {{10.1530/acta.0.1270027}},
  volume       = {{127}},
  year         = {{1992}},
}