TY - JOUR T1 - Desensitization of Histamine H<sub>1</sub> Receptor-Mediated Cyclic GMP Formation in Mouse Neuroblastoma Cells JF - Molecular Pharmacology JO - Mol Pharmacol SP - 462 LP - 471 VL - 15 IS - 3 AU - JOHN E. TAYLOR AU - ELLIOTT RICHELSON Y1 - 1979/05/01 UR - http://molpharm.aspetjournals.org/content/15/3/462.abstract N2 - Histamine H1 receptor-mediated cyclic GMP formation by intact mouse neuroblastoma cells (clone N1E-115) was attenuated by prolonged exposure to histamine. This desensitization was dependent upon the concentration of histamine and at 10 µM the half-time was ≃9 min, whereas the half-time for resensitization in the absence of histamine was ≃13 min. The order of potency for agonist-induced desensitization correlated with the order of potency for stimulating the H1 receptor (histamine &gt; 2-methylhistamine; 4-methylhistamine, no effect). Pyrilamine (50 nM) was more potent than metiamide (15 µM) in blocking desensitization by histamine. The ED50 for activation and for desensitization by histamine of the receptor-mediated response was approximately equal to its KA for the H1 receptor. Omission of Ca++ in the medium prevented cyclic GMP formation, but did not affect desensitization, suggesting that cyclic GMP formation was not required for the development of the desensitized state. Desensitization was temperature-dependent and marked inhibition of protein synthesis did not affect desensitization or its reversal. Finally, the ED50's for histamine-stimulated cyclic GMP formation in control and in partially desensitized cells were similar while the maximum response was reduced. ACKNOWLEDGMENTS The authors thank Drs. J. R. Blinks and F. G. Prendergast for helpful discussions. ER -