Constitutive activity of the histamine H1 receptor reveals inverse agonism of histamine H1 receptor antagonists

Transient expression of the wild-type human histamine H-1 receptor in SV40-immortalised African green monkey kidney cells resulted in an agonist-independent elevation of the basal levels of the second messenger inositoltrisphospate. Several histamine H-1 receptor antagonists, including the therapeutically used anti-allergies cetirizine, loratadine and epinastine reduced this constitutive histamine H-1 receptor activity, inverse agonism, i.e., stabilisation of an inactive conformation of the human histamine H-1 receptor, may therefore be a key component of the anti-allergic mechanism of action of clinically used antihistamines. (C) 2000 Elsevier Science B.V. All rights reserved.