Presynaptic H3 autoreceptors modulate histamine synthesis through cAMP pathway
Presynaptic H3 autoreceptors modulate histamine synthesis through cAMP pathway
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DOI：
10.1124/mol.61.1.239
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发表时间：
2002-01-01
影响因子：
3.6
通讯作者：
Blanco, I
中科院分区：
文献类型：
--
作者：
Gomez-Ramirez, J;Ortiz, J;Blanco, I
组胺H-3受体调节组胺的合成，尽管对所涉及的转导机制知之甚少。为了研究这个问题，我们已经使用了大鼠大脑皮层miniprism的制备，其中组胺的合成可以通过去极化和H-3受体配体来调节。当在存在毛喉素，二丁酰-cAMP，或3-异丁基-1-甲基黄嘌呤（IBMX）的情况下孵育的miniprism，组胺的合成分别刺激34，29和47%。这些刺激作用可被选择性cAMP蛋白激酶阻断剂Rp-cAMPs（Rp-adenosine 3 '，5'-cyclic monophosphothiocate triethane）阻断。用H-3受体激动剂imetit预孵育可防止IBMX-（100%阻断）和毛喉素-（70%阻断）诱导的组胺合成刺激。在1 mM IBMX或30 mM钾的存在下，H-3反向激动剂硫代哌丁胺增强组胺合成（分别为+47和+45%）。同样，H-3拮抗剂clobenpropit在30 mM钾（+ 59%）的存在下增强组胺合成。cAMP依赖性蛋白激酶阻断剂Rp-cAMPs和PKI 14 -22可分别削弱硫代哌丁胺和氯苄丙酸的作用。这些结果表明，腺苷酸环化酶-蛋白激酶A途径参与组胺能神经末梢中存在的H-3自身受体对组胺合成的调节。
Histamine H-3 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 H-3 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 blocker Rp-adenosine 3',5'-cyclic monophosphothioate triethylamine (Rp-cAMPs). Preincubation with the H-3 receptor agonist imetit prevented IBMX- (100% blockade) and forskolin- (70% blockade) induced stimulation of histamine synthesis. The H-3 inverse agonist thioperamide enhanced histamine synthesis in the presence of 1 mM IBMX or 30 mM potassium (+47 and +45%, respectively). Similarly, the H-3 antagonist clobenpropit enhanced histamine synthesis in the presence of 30 mM potassium (+ 59%). The cAMP-dependent protein kinase blockers Rp-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 H-3 autoreceptors present in histaminergic nerve terminals.