Document Detail


Somatostatin depleting potency of cysteamine-related thiols and amines in the rat: structure-activity relation.
MedLine Citation:
PMID:  1359114     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Cysteamine, a potent duodenal ulcerogen, stimulates gastric acid and gastrin secretion and decreases immunoreactive somatostatin (IRS) from the gut and hypothalamus of the rat. To elucidate the structural requirements for this effect, we tested a series of cysteamine analogs for their IRS decreasing activity in comparison with their nucleophilic and reducing potencies. Adult female rats were sacrificed 4 hr after p.o. administration of the test chemicals given in molar equivalents to 30 mg/100 g of cysteamine-HCl. IRS decreasing activity in gastric mucosa, expressed as percentage of controls is listed in descending order: cystamine (55%), cysteamine (59%), 2-dimethylaminethanethiol (59%), ethylamine (66%), 1,3-propanedithiol (70%), propylamine (75%) and 3-aminothiophenol (79%). The following thiols and amines had no IRS decreasing effect (80% of controls): L-cysteine, ethanethiol, 1-propanethiol, penicillamine, dimercaprol, 1-4-dithiothreitol, ethanolamine, propionitrile, n-butyronitrile, o-, m- or p-aminophenol. The aryl 2-, 3- or 4-aminothiophenols, unlike most of their aminophenol analogs also decreased immunoreactive prolactin in the pituitary by 38 to 78%. IRS decreasing activity was independent of the reducing potency of cysteamine derivatives but was correlated significantly (r = 0.793, P < .01) with electron affinity of -SH, -NH2, -OH and -CN radicals in terminal alkyl chemicals. The structural requirement for decreasing activity is the presence of either -SH and -NH2 on a 2 to 3 carbon alkyl or aryl molecule. Both radicals when present together increase potency.(ABSTRACT TRUNCATED AT 250 WORDS)
Authors:
S Szabo; S Reichlin; J A Bollinger-Gruber; A Brown
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Publication Detail:
Type:  Comparative Study; Journal Article    
Journal Detail:
Title:  The Journal of pharmacology and experimental therapeutics     Volume:  263     ISSN:  0022-3565     ISO Abbreviation:  J. Pharmacol. Exp. Ther.     Publication Date:  1992 Nov 
Date Detail:
Created Date:  1992-12-08     Completed Date:  1992-12-08     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0376362     Medline TA:  J Pharmacol Exp Ther     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  752-6     Citation Subset:  IM    
Affiliation:
Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts.
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MeSH Terms
Descriptor/Qualifier:
Amines / pharmacology*
Aniline Compounds / pharmacology
Animals
Cystamine / pharmacology
Cysteamine / analogs & derivatives*,  pharmacology
Down-Regulation
Ethylamines / pharmacology
Female
Gastric Mucosa / drug effects*,  metabolism
Propylamines / pharmacology
Rats
Rats, Sprague-Dawley
Somatostatin / metabolism*
Structure-Activity Relationship
Sulfhydryl Compounds / pharmacology*
Chemical
Reg. No./Substance:
0/Amines; 0/Aniline Compounds; 0/Ethylamines; 0/Propylamines; 0/Sulfhydryl Compounds; 51-85-4/Cystamine; 51110-01-1/Somatostatin; 60-23-1/Cysteamine; 75-04-7/ethylamine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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