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The role of histamine H1, H2 and H3 receptors in the stimulation of NT‐3 synthesis in astrocytes
Author(s) -
CarmanKrzan Marija,
Mele Tina,
Juric Damijana Mojca
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.1003.7
Subject(s) - histaminergic , adenylyl cyclase , receptor , pertussis toxin , stimulation , medicine , intracellular , chemistry , endocrinology , histamine , protein kinase c , forskolin , signal transduction , second messenger system , biology , g protein , microbiology and biotechnology , biochemistry
Neurotrophin‐3 (NT‐3) is produced by astrocytes, in addition to neurons, and monoamine neurotransmitters play a role in controlling NT‐3 synthesis. We evaluated the active involvement of histamine receptors and intracellular mechanisms in the regulation of NT‐3 production by HA. HA (1 μM) significantly and transiently elevated NT‐3 mRNA levels by 2.2‐fold after 30 min of incubation following by 2.1‐fold increase in NT‐3 intracellular levels after 6 h. Its stimulation was partly inhibited by selective H 1 , H 2 and H 3 antagonists. NT‐3 levels in astrocytes were increased by selective H 1 , H 2 and H 3 agonists as well as by adenylyl cyclase activation, PKA activation, PKC activation and mobilization of intracellular Ca 2+ . HA‐induced increase in NT‐3 cellular levels were significantly reduced by H‐89, staurosporin, KN‐62 and desensitizing pretreatment with TPA. MAP kinase cascade inhibitor PD98059 completely blocked the stimulatory action of HA and all selective agonists. Using quantitative RT‐PCR we confirmed that cultured rat cortical astrocytes express not only H 1 and H 2 receptors already identified by radioligand binding studies but also H 3 receptors which were sensitive to pertussis toxin. In conclusion, the synthesis of astrocytic NT‐3 stimulated by HA is an adaptable process using several parallel histaminergic pathways using H 1 ‐, H 2 ‐, and H 3 ‐receptor pathways. The observed H 1 , H 2 and H 3 receptor crosstalk in histaminergic regulation of NT‐3 leads to the convergence of these pathways at the level of MAP kinase activity which in the next step triggers the increased expression and subsequently the synthesis of NT‐3 in astrocytes.