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  • Title: Identification of adenylate cyclase-coupled histamine H2 receptors in guinea pig tracheal smooth muscle cells in culture and the effect of dexamethasone.
    Author: Florio C, Flezar M, Martin JG, Heisler S.
    Journal: Am J Respir Cell Mol Biol; 1992 Dec; 7(6):582-9. PubMed ID: 1333244.
    Abstract:
    Histamine acts on airway contractile elements through at least two different receptor subtypes: H1, which mediates Ca(2+)-dependent contraction, and H2, which stimulates cyclic adenosine monophosphate (cAMP) synthesis and possibly relaxation. The aim of this study was to determine the relative contribution of the different receptor subtypes to histamine-stimulated cAMP production by guinea pig tracheal smooth muscle (GPTSM) cells in primary culture. Histamine and N-alpha-methylhistamine induced concentration-dependent cAMP synthesis; these effects were entirely blocked by 10(-4) M cimetidine, an H2-receptor antagonist, whereas 10(-6) M thioperamide, a selective H3 blocker, was ineffective. The H3 agonist, R-(alpha)-methylhistamine, did not stimulate cAMP synthesis. Triprolidine, an H1 antagonist, did not modify histamine (10(-5) M)-stimulated cAMP synthesis. Histamine (10(-5) M) doubled [Ca2+]i in GPTSM. A 24-h pretreatment of GPTSM cells with 10(-6) M dexamethasone enhanced cAMP synthesized in response to 10(-5) M histamine and to 5 x 10(-6) M forskolin but did not significantly alter either the affinity or the binding capacity for [3H]-tiotidine, an H2-receptor antagonist. These results indicate that GPTSM cells in culture express H2 but not H3 receptors, which are linked to adenylate cyclase; their functional expression does not seem to be modulated by the concurrent activation of H1 receptors, whose presence in GPTSM is evidenced by a histamine-stimulated increase in [Ca2+]i. The most likely site of action of dexamethasone in enhancing histamine-stimulated cAMP synthesis is at the level of adenylate cyclase since the steroid had no effect on the H2 receptor itself.
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