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. 1993 Jun;109(2):353–359. doi: 10.1111/j.1476-5381.1993.tb13577.x

Desensitization of histamine H1 receptor-mediated inositol phosphate production in HeLa cells.

D R Bristow 1, M R Zamani 1
PMCID: PMC2175704  PMID: 8358540

Abstract

1. Histamine stimulated the accumulation of total [3H]-inositol phosphates (IPn) in control HeLa cells with an EC50 of 3.7 +/- 0.7 microM in the presence of 10 mM LiCl. The maximum response to histamine after 15 min incubation was 43 +/- 5% over basal accumulation and occurred at a concentration of 1 mM histamine. 2. The histamine-induced IPn production in HeLa cells was confirmed as H1 receptor-mediated, since the H1 antagonist mepyramine (10(-6) M) inhibited the histamine response (10(-4) M) by 83 +/- 7%, whereas the H2 antagonist, ranitidine (10(-4) M), and H3 antagonist, thioperamide (10(-6) M), were ineffective. 3. Histamine (10(-4) M) pretreatment of HeLa cells for 30 min desensitized the subsequent histamine-induced IPn accumulation. The desensitized cells accumulated IPn in response to histamine with an EC50 of 1.7 +/- 0.7 microM after 15 min incubation. The maximum histamine-induced IPn accumulation at 10(-4) M was 19 +/- 5% over basal and was significantly lower (P < 0.03) than the maximum response in control cells. 4. The desensitization of histamine-induced IPn accumulation was time-dependent and, at a desensitizing histamine concentration of 10(-4) M, the half-maximal attenuation occurred after approximately 9 min and maximum desensitization was achieved by 15-20 min. The desensitization of the IPn accumulation was a reversible phenomenon and full recovery of the response occurred 150 min after the removal of the desensitizing histamine-containing medium. The half-time for the recovery of the histamine-induced response was estimated at 120 min.(ABSTRACT TRUNCATED AT 250 WORDS)

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Selected References

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