| Bradykinin metabolism in rat and sheep nasal secretions. | |
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MedLine Citation:
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PMID: 7562432 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The nasal secretions are the first barrier that nasally administered drugs encounter. Therefore, the characterization of peptide metabolism in the nasal secretions is essential to predict nasal peptide bioavailability. Metabolism of bradykinin was measured in rat and sheep nasal secretions to estimate the extent of degradation of nasally administered peptide compounds. A single-pass, in situ nasal perfusion technique was employed to collect secretions for the investigation of peptide metabolism in rat nasal secretions. The protein content, mucin concentration, and degree of bradykinin metabolism in perfusate aliquots collected over a 2-h period showed that the early perfusate fractions contained most of the active secretory materials. Evidence of continuous mucus secretion and plasma extravasation was found in the nasal perfusate throughout the entire collection period. Sheep nasal secretions were collected with a cotton pledget inserted into the nasal cavity. Bradykinin and its fragments were degraded by carboxypeptidases and endopeptidases present in both rat and sheep nasal secretions. Hydrolysis of Phe5-Ser6 was the major metabolism pathway of bradykinin in the rat nasal perfusate, whereas in sheep nasal secretions, hydrolysis of the Pro7-Phe8 and Phe8-Arg9 bonds also occurred. Evidence of angiotensin converting enzyme, carboxypeptide N, and aminopeptidase activity was identified in the rat nasal perfusate with specific substrates and inhibitors. The activity of these and other enzymes in the nasal secretions may significantly limit the bioavailability of nasally administered peptide drugs prior to their exposure to the nasal mucosal tissues. |
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Authors:
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F Y Chung; M D Donovan |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of pharmaceutical sciences Volume: 84 ISSN: 0022-3549 ISO Abbreviation: J Pharm Sci Publication Date: 1995 Jul |
Date Detail:
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Created Date: 1995-11-22 Completed Date: 1995-11-22 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 2985195R Medline TA: J Pharm Sci Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 829-34 Citation Subset: IM |
Affiliation:
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Division of Pharmaceutics, College of Pharmacy, University of Iowa, Iowa City 52242, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Biological Availability Bradykinin / metabolism* Kinetics Male Mucins / metabolism Nasal Mucosa / metabolism* Proteins / metabolism Rats Rats, Sprague-Dawley Sheep Time Factors |
| Chemical | |
Reg. No./Substance:
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0/Mucins; 0/Proteins; 58-82-2/Bradykinin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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