Characterisation of new efaroxan derivatives for use in purification of imidazoline-binding sites.
Eur J Pharmacol
; 355(1): 67-76, 1998 Aug 14.
Article
en En
| MEDLINE
| ID: mdl-9754940
ABSTRACT
The insulin secretagogue activity of certain imidazoline compounds is mediated by a binding site associated with ATP-sensitive K+ (K(ATP)) channels in the pancreatic beta-cell. We describe the effects of a series of structural modifications to efaroxan on its activity at this site. Substitution of amino-, nitro- or azide- groups onto the 5-position of the benzene ring of efaroxan did not significantly affect the functional interaction of the ligand with the islet imidazoline binding site. Modification of the imidazoline ring to an imidazole to generate 2-(2-ethyl-2,3-dihydrobenzo[b]furan-2-yl)-1H-imidazole (KU14R) resulted in loss of secretagogue activity. Indeed, this reagent appeared to act as an imidazoline antagonist since it blocked the secretory responses to imidazoline compounds and also inhibited the blockade of beta-cell K(ATP) channels by efaroxan in patch clamp experiments. Application of KU14R alone resulted in a modest reduction in K(ATP) channel opening, suggesting that it may display weak partial agonism, at least in patch-clamp experiments.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Receptores de Droga
/
Benzofuranos
/
Islotes Pancreáticos
/
Antagonistas Adrenérgicos alfa
/
Imidazoles
Límite:
Animals
Idioma:
En
Revista:
Eur J Pharmacol
Año:
1998
Tipo del documento:
Article
País de afiliación:
Reino Unido