PT  - JOURNAL ARTICLE
AU  - Jordi Gomez-Ramirez
AU  - Jordi Ortiz
AU  - Isaac Blanco
TI  - Presynaptic H<sub>3</sub> Autoreceptors Modulate Histamine Synthesis through cAMP Pathway
AID  - 10.1124/mol.61.1.239
DP  - 2002 Jan 01
TA  - Molecular Pharmacology
PG  - 239--245
VI  - 61
IP  - 1
4099  - http://molpharm.aspetjournals.org/content/61/1/239.short
4100  - http://molpharm.aspetjournals.org/content/61/1/239.full
SO  - Mol Pharmacol2002 Jan 01; 61
AB  - 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.