The effect of desensitization on the antagonism of the histamine response by phenoxybenzamine
Kenakin, T.P.; Cook, D.A.
Molecular Pharmacology 17(3): 309-313
1980
ISSN/ISBN: 0026-895X PMID: 7393211 Document Number: 156360
Blockade of the histamine response by phenoxybenzamine was studied in both desensitized and nondesensitized preparations of the longitudinal smooth muscle of the guinea pig ileum. Desensitization to histamine had little effect on the parallel shift in the dose-response curve to histamine produced by phenoxybenzamine but did affect the antagonism of the maximum histamine response by this agent. Since there is evidence that this antagonist interacts at the receptor, desensitization of the histamine H1 receptor in this preparation apparently involves changes at the receptor level, possibly alterations in conformation. The results are described in terms of the cyclic model of desensitization proposed and the metaphilic effect.