The interaction of U-73122 with the histamine H1 receptor: implications for the use of U-73122 in defining H1 receptor-coupled signalling pathways.
Naunyn Schmiedebergs Arch Pharmacol
; 362(6): 555-8, 2000 Dec.
Article
em En
| MEDLINE
| ID: mdl-11138848
ABSTRACT
U-73122, an N-aminosteroid homologue of N-ethylmaleimide (NEM), widely used as an inhibitor of phospholipase C, was found to be a potent inhibitor (IC50 5.5+/-0.5 microM) of the binding of [3H]mepyramine to guinea-pig cerebellar membranes. The succinimido analogue, U-73343, also inhibited the binding of [3H]mepyramine (estimated IC50 24+/-1 microM), but NEM was only a weak inhibitor, even at 10 mM. The interaction of U-73122 and U-73343 with the H1 receptor was effectively irreversible, on the time-scale of the experiment. There is no indication that reaction with a receptor thiol residue is involved in the binding of U-73122, since preincubation of membranes with 2 mM NEM did not significantly increase the IC50 for the inhibition of [3H]mepyramine binding by U-73122. We conclude that U-73122 binds to the histamine H1 receptor in the concentration range in which it acts as an inhibitor or PLC. This compromises the use of U-73122 to provide evidence that an H1 agonist action is mediated via PLC. The tight binding of U-73343 to the receptor appears to be primarily a function of the hydrophobic nature of the compound.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pirrolidinonas
/
Receptores Histamínicos H1
/
Estrenos
Limite:
Animals
Idioma:
En
Ano de publicação:
2000
Tipo de documento:
Article