Histamine up-regulates phosphodiesterase 4 activity and reduces prostaglandin E2-inhibitory effects in human neutrophils

被引：13

作者：

Dasí, FJ ^{[1
]}

Ortiz, JL ^{[1
]}

Cortijo, J ^{[1
]}

Morcillo, EJ ^{[1
]}

机构：

[1] Univ Valencia, Fac Med & Odontol, Dept Farmacol, Valencia 46010, Spain

来源：

INFLAMMATION RESEARCH | 2000年 / 49卷 / 11期

关键词：

histamine; phosphodiesterase isoenzymes; phosphodiesterase; 4; up-regulation; human neutrophils;

D O I：

10.1007/s000110050637

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Objective: To investigate whether histamine produces up-regulation of phosphodiesterase (PDE) activity with functional consequences in human peripheral blood neutrophils. Methods: PDE activity was studied by a radioisotopic method following anion-exchange chromatography. Reverse transcriptase-polymerase chain reaction (RT-PCR) was used for detection of mRNA transcripts of PDE4 subtypes. Cyclic AMP (cAMP) levels were measured by enzyme-immunoassay, and superoxide generation by cytochrome c reduction. Treatment: Neutrophils were incubated for 4 h with histamine (1 muM) Results: PDE4 was the only isoenzyme activity increased in treated neutrophils. Kinetic analysis showed a similar to1.5-fold increase in V-max without alteration of K-m values, cAMP content in treated cells was higher than resting values (0.52 +/- 0.07 vs. 2.75 +/- 0.31 pmol/10(6) cells). RT-PCR showed increased expression of mRNA transcripts for PDE4B in histamine-treated cells. Functionally, up-regulation of PDE4 reduced the inhibition by prostaglandin E-2 of zymosan-induced superoxide generation. Conclusion: Histamine up-regulates PDE4 activity and produces heterologous desensitisation of human neutrophils.

引用

页码：600 / 609

页数：10

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