JPET

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Zini, S.
Right arrow Articles by Ben-Ari, Y.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Zini, S.
Right arrow Articles by Ben-Ari, Y.

Nucleotides modulate the low affinity binding sites for [3H]glibenclamide in the rat brain

S Zini, R Zini and Y Ben-Ari

Laboratoire de Neurobiologie et Physiopathologie du Developpement, Institut National de la Sante et de la Recherche Medicale U29, Paris, France.

Receptors for hypoglycemic sulfonylureas, such as glibenclamide, are commonly linked to the activity of ATP-sensitive K+ channels (K-ATP). High and low affinity binding sites for glibenclamide were described previously in numerous tissues. High affinity binding sites have been thought to be responsible of the modulation of K-ATP, but new evidences suggest that low affinity ones could also regulate these channels. In order to clarify the properties of the two binding sites, with respect to their interaction with K-ATP, we characterized biochemically and pharmacologically [3H]glibenclamide binding in the rat brain cortex. Competitive inhibition plots with [3H]glibenclamide performed on membranes of adult and neonatal rat brain cortex exhibited a biphasic pattern with similar binding parameters, indicating the presence of two similar binding sites in adult as well as in neonatal animals. Membranes of adult rat cortex treated with thiol groups modifying agents, N-ethylmaleimide or 1,4-dithiothreitol, increased the inhibition constant of glibenclamide for the low affinity binding sites (K(i)L) by about 4-fold. The divalent cations Mg++ and Ca++ also increased K(i)L by 3- to 6-fold and enhanced the low affinity binding capacity (BmaxL) by 55 and 103%, respectively, both cations increasing BmaxL by 144%. Among the numerous nucleotides studied, adenine and guanidine triphosphate nucleotides were the most potent to affect the low affinity binding sites. ATP, ADP, GTP and respective nonhydrolysable nucleotides increased K(i)L by 7- to 12-fold and decreased BmaxL by 10 to 30%. The effects of nucleotides were not Mg++ dependent.(ABSTRACT TRUNCATED AT 250 WORDS)

Volume 264, Issue 2, pp. 701-708, 02/01/1993
Copyright © 1993 by American Society for Pharmacology and Experimental Therapeutics




This article has been cited by other articles:


Home page
 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
B. E. Levin, A. A. Dunn-Meynell, and V. H. Routh
Brain glucose sensing and body energy homeostasis: role in obesity and diabetes
Am J Physiol Regulatory Integrative Comp Physiol, May 1, 1999; 276(5): R1223 - R1231.
[Abstract] [Full Text] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 1993 by the American Society for Pharmacology and Experimental Therapeutics.