Role of PKA and PKC in histamine H1 receptor-mediated activation of catecholamine neurotransmitter synthesis

被引:12
作者
Moniri, Nader H.
Booth, Raymond G. [1 ]
机构
[1] Univ Florida, Dept Med Chem, Coll Pharm, Gainesville, FL 32610 USA
[2] Univ N Carolina, Sch Pharm, Div Med Chem & Nat Prod, Chapel Hill, NC 27599 USA
关键词
adrenal chromaffin cell; catecholamine; histamine; H-1; receptor; protein kinase C; tyrosine hydroxylase; striatum;
D O I
10.1016/j.neulet.2006.08.051
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Activation of the histamine H, receptor stimulates tyrosine hydroxylase (TH) to increase catecholamine neurotransmitter synthesis in mammalian brain and adrenal tissues. Histamine non-selectively activates both H-1-linked phospholipase (PL) C/mositol phosphates (IP)/diacylglycerol (DAG) signaling and adenylyl cyclase (AC)/adenosine 3',5'-cyclic monophosphate (cAMP) signaling, confounding determination of signaling events involved in HI-mediated TH activation. This research uses two new functionally-selective H-1 agonists, cis-PAB and trans-PAT, that selectively activate H-1/PLC/IP/DAG and H-1/AC/cAMP signaling, respectively, to characterize H-1-mediated activation of TH in rat striatum and bovine adrenal chromaffin (BAC) cells. Histamine, cis-PAB, and trans-PAT produced a two-fold maximal TH activation by an H, receptor mechanism in rat striatum and BAC cells. Histamine is more potent and efficacious in BAC cells (EC50 similar to 0.2 mu M, E-max similar to 200% basal) versus rat striatum (EC50 similar to 0.4 mu M; E-max similar to 150%). Cis-PAB and trans-PAT are more potent in rat striatum (EC50 similar to 0-1 mu M forboth agonists) versus BAC cells (EC50 similar to 1.0 mu M for both), with similar efficacy in both preparations (E-max similar to 160% for both agonists). Signaling studies in BAC cells revealed that protein kinase (PK) A but not PKC is involved in H-1-mediated TH activation by trans-PAT and histamine, while, both PKA and PKC are involved for cis-PAB. Results for cis-PAB suggest H-1/PLC/IP/DAG/PKC signaling activates PKA, downstream of cAMP formation, indicating apparent direct activation of PKA by PKC. (c) 2006 Published by Elsevier Ireland Ltd.
引用
收藏
页码:249 / 253
页数:5
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