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Different role of cAMP dependent protein kinase and CaMKII in H3 receptor regulation of histamine synthesis and release.

Abstract：

:Histamine H(3) autoreceptors induce a negative feedback on histamine synthesis and release. While it is known that cAMP/cAMP dependent protein kinase (PKA) and Ca(2+)/CaMKII transduction pathways mediate H(3) effects on histamine synthesis, the pathways regulating neuronal histamine release are poorly known. Given the potential use of H(3) ligands in cognitive diseases, we have developed a technique for the determination of H(3) effects on histamine synthesis and release in brain cortical miniprisms. Potassium-induced depolarization effects were impaired by blockade of calcium entry through N and P/Q channels, as well as of CaMKII, but release was not affected by activators or inhibitors of the cAMP/PKA pathway (1-methyl-3-isobutylxanthine (IBMX), N6,2'-O-dibutyryladenosine 3',5'-cyclic monophosphate sodium salt (db-cAMP) or myristoyl PKA inhibitor peptide 14-22 (PKI(14-22)). In contrast, forskolin stimulated histamine release, although independently of PKA. Stimulation of histamine H(3) receptors with the agonist imetit markedly reduced the depolarization increase of histamine release, apparently through P/Q calcium channel inhibition. The H(3) antagonist/inverse agonist thioperamide modestly stimulated histamine release. Thioperamide effect on release was not modified by the PKA inhibitor PKI(14-22), but it was blocked by the CaMKII inhibitor KN-62. These results indicate that H(3) autoreceptors regulate neuronal histamine release (1) independently of the cAMP/PKA cascade, and (2) through modulation of calcium entry and CaMKII activation during depolarization.

journal_name

Neuroscience

journal_title

Neuroscience

authors

Moreno-Delgado D,Gómez-Ramírez J,Torrent-Moreno A,González-Sepúlveda M,Blanco I,Ortiz J

doi

10.1016/j.neuroscience.2009.08.068

subject

Has Abstract

pub_date

2009-12-15 00:00:00

pages

1244-51

issue

3

eissn

0306-4522

issn

1873-7544

pii

S0306-4522(09)01380-3

journal_volume

164

pub_type

杂志文章

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