Document Detail


Stimulation of insulin secretion by imidazoline compounds is not due to interaction with non-adrenoceptor idazoxan binding sites.
MedLine Citation:
PMID:  8095415     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
1. The potency of interaction of several imidazoline compounds with non-adrenoceptor idazoxan binding sites (NAIBS) in rat liver membranes was compared with their ability to alter insulin secretion from rat pancreatic islets. 2. NAIBS could be labelled specifically with [3H]-idazoxan in both rat liver membranes and in rat islet homogenates. Liver binding sites exhibited a KD for [3H]-idazoxan of 24 nM and a Bmax of 264 fmol mg-1 protein. 3. Binding of [3H]-idazoxan to NAIBS in rat liver membranes was displaced effectively by unlabelled idazoxan (IC50 0.1 microM) and by UK14304 (IC50 0.5 microM). However, two other imidazoline compounds efaroxan and RX821002, which are related in structure to idazoxan, were much less effective as displacers. 4. In insulin secretion experiments, the ATP-sensitive potassium channel agonist diazoxide (250 microM) was able to suppress the rise in insulin secretion induced by 20 mM glucose. Both efaroxan and RX821002 (100 microM) antagonized the inhibitory effect of diazoxide on glucose-induced insulin secretion. By contrast, neither idazoxan (100 microM) nor UK14304 (50 microM), was able to overcome significantly the inhibitory effect of diazoxide. 5. The ability of 100 microM efaroxan to antagonize the suppression of insulin secretion mediated by diazoxide, was not prevented by idazoxan (up to 100 microM) or by UK14304 (up to 50 microM). 6. The results indicate that the stimulatory effects of imidazoline compounds on insulin secretion are not due to interaction with NAIBS similar to those present in rat liver.
Authors:
C A Brown; A C Loweth; S A Smith; N G Morgan
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Publication Detail:
Type:  Comparative Study; In Vitro; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  British journal of pharmacology     Volume:  108     ISSN:  0007-1188     ISO Abbreviation:  Br. J. Pharmacol.     Publication Date:  1993 Feb 
Date Detail:
Created Date:  1993-04-09     Completed Date:  1993-04-09     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7502536     Medline TA:  Br J Pharmacol     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  312-7     Citation Subset:  IM    
Affiliation:
Department of Biological Sciences, Keele University, Staffs.
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MeSH Terms
Descriptor/Qualifier:
Adrenergic alpha-Agonists / pharmacology
Adrenergic alpha-Antagonists / pharmacology
Animals
Binding Sites / drug effects
Imidazoles / pharmacology*
Insulin / secretion*
Islets of Langerhans / drug effects*,  metabolism,  secretion
Liver / drug effects*,  metabolism
Male
Membranes / drug effects,  metabolism
Radioligand Assay
Rats
Rats, Wistar
Receptors, Adrenergic, alpha / drug effects*
Receptors, Drug / drug effects*
Grant Support
ID/Acronym/Agency:
//Wellcome Trust
Chemical
Reg. No./Substance:
0/Adrenergic alpha-Agonists; 0/Adrenergic alpha-Antagonists; 0/Imidazoles; 0/Receptors, Adrenergic, alpha; 0/Receptors, Drug; 0/idazoxan receptor; 11061-68-0/Insulin
Comments/Corrections

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


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