TY - JOUR T1 - Specific Desensitization of Histamine H<sub>1</sub> Receptor-Mediated [<sup>3</sup>H]Glycogen Hydrolysis in Brain Slices JF - Molecular Pharmacology JO - Mol Pharmacol SP - 331 LP - 338 VL - 20 IS - 2 AU - TAM THANH QUACH AU - ANNE-MARIE DUCHEMIN AU - CHRISTIANE ROSE AU - JEAN-CHARLES SCHWARTZ Y1 - 1981/09/01 UR - http://molpharm.aspetjournals.org/content/20/2/331.abstract N2 - In slices from mouse cerebral cortex, histamine elicits in a concentration-dependent manner the hydrolysis of [3H]glycogen previously synthesized from [3H]glucose, a response mediated by H1 receptors. Desensitization of this glycogenolytic response occurs when slices are incubated with 50 µM histamine and is characterized by a rightward shift of the concentration-response curve (EC50 = 32 ± 1 µM instead of 4 ± 1 µM) without significant change in the maximal glycogenolysis. Desensitization occurs with a half-time of about 20 min, and the initial responsiveness is gradually recovered within 1 hr. Recovery is not impaired in the presence of cycloheximide, a protein synthesis inhibitor. Desensitization to the glycogenolytic action of histamine seems to be a selective process: (a) it results from stimulation of H1 receptors, since 2-thiazolylethylamine, an H1-receptor agonist (but not dimaprit, an H2-receptor agonist) shares the desensitizing action of histamine; (b) only the glycogenolytic response to histamine is desensitized, whereas responsiveness to other glycogenolytic agents (noradrenaline, serotonin, adenosine, dibutyryl cyclic AMP) is not modified. Following exposure of slices to histamine, the binding of [3H]mepyramine to H1 receptors is significantly modified. The change consists of a 20% decrease in the Bmax of the [3H]antihistamine without significant change in either its Kd or the Ki of histamine. ER -