Densensitization of histamine H1 receptor-mediated cyclic GMP formation in mouse neuroblastoma cells

J. E. Taylor, E. Richelson

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

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 10μM 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 > 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 K(A) 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.

Original languageEnglish (US)
Pages (from-to)462-471
Number of pages10
JournalMolecular Pharmacology
Volume15
Issue number3
StatePublished - 1979

ASJC Scopus subject areas

  • Pharmacology

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