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Research ArticleArticle

Presynaptic H3 Autoreceptors Modulate Histamine Synthesis through cAMP Pathway

Jordi Gomez-Ramirez, Jordi Ortiz and Isaac Blanco
Molecular Pharmacology January 2002, 61 (1) 239-245; DOI: https://doi.org/10.1124/mol.61.1.239
Jordi Gomez-Ramirez
Department of Biochemistry and Molecular Biology, School of Medicine, Universitat Autònoma de Barcelona, Bellaterra, Spain.
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Jordi Ortiz
Department of Biochemistry and Molecular Biology, School of Medicine, Universitat Autònoma de Barcelona, Bellaterra, Spain.
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Isaac Blanco
Department of Biochemistry and Molecular Biology, School of Medicine, Universitat Autònoma de Barcelona, Bellaterra, Spain.
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Abstract

Histamine H3 receptors modulate histamine synthesis, although little is known about the transduction mechanisms involved. To investigate this issue, we have used a preparation of rat brain cortical miniprisms in which histamine synthesis can be modulated by depolarization and by H3 receptor ligands. When the miniprisms were incubated in presence of forskolin, dibutyryl-cAMP, or 3-isobutyl-1-methylxanthine (IBMX), histamine synthesis was stimulated in 34, 29, and 47%, respectively. These stimulations could be prevented by the selective cAMP protein kinase blockerRp-adenosine 3′,5′-cyclic monophosphothioate triethylamine (Rp-cAMPs). Preincubation with the H3 receptor agonist imetit prevented IBMX- (100% blockade) and forskolin- (70% blockade) induced stimulation of histamine synthesis. The H3 inverse agonist thioperamide enhanced histamine synthesis in the presence of 1 mM IBMX or 30 mM potassium (+47 and +45%, respectively). Similarly, the H3 antagonist clobenpropit enhanced histamine synthesis in the presence of 30 mM potassium (+ 59%). The cAMP-dependent protein kinase blockersRp-cAMPs and PKI14–22 could impair the effects of thioperamide and clobenpropit, respectively. These results indicate that the adenylate cyclase-protein kinase A pathway is involved in the modulation of histamine synthesis by H3 autoreceptors present in histaminergic nerve terminals.

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Molecular Pharmacology: 61 (1)
Molecular Pharmacology
Vol. 61, Issue 1
1 Jan 2002
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Research ArticleArticle

Presynaptic H3 Autoreceptors Modulate Histamine Synthesis through cAMP Pathway

Jordi Gomez-Ramirez, Jordi Ortiz and Isaac Blanco
Molecular Pharmacology January 1, 2002, 61 (1) 239-245; DOI: https://doi.org/10.1124/mol.61.1.239

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Research ArticleArticle

Presynaptic H3 Autoreceptors Modulate Histamine Synthesis through cAMP Pathway

Jordi Gomez-Ramirez, Jordi Ortiz and Isaac Blanco
Molecular Pharmacology January 1, 2002, 61 (1) 239-245; DOI: https://doi.org/10.1124/mol.61.1.239
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