G-Protein inwardly rectifying potassium channels are involved in the hypotensive effect of I1-imidazoline receptor selective ligands
G-Protein inwardly rectifying potassium channels are involved in the hypotensive effect of I1-imidazoline receptor selective ligands
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G蛋白内向整流钾通道参与I1-咪唑啉受体选择性配体的降血压作用
DOI：
10.1097/hjh.0b013e3282f5ed44
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发表时间：
2008
影响因子：
4.9
通讯作者：
J. Feldman
中科院分区：
文献类型：
--
作者：
Guata Yoro Sy;D. Urošević;L. Fellmann;H. Greney;P. Bousquet;J. Feldman
目的研究G蛋白内向整流钾通道（GIRK）在脑池注射咪唑啉类药物引起的降压反应中的作用。方法和结果脑池内注射I1-咪唑啉受体（I1 R）选择性配体LNP 509（30 μg/kg）和LNP 640（2 μg/kg）（阈下剂量）以及GIRK通道开放剂氟吡汀（30 μg/kg）对平均动脉血压（MAP）无影响。然而，LNP 509和LNP 640在氟吡汀预处理的家兔中引起显著的降压反应（分别为-17 ± 2和-18 ± 1 mmHg，P < 0.05）。注射较高剂量的LNP 509（200 μg/kg）或LNP 640（10 μg/kg）可显著降低幼稚兔的MAP（分别为-45 ± 3和-39 ± 2 mmHg，P < 0.05）。用GIRK通道阻断剂tertiapin-Q（10 μg/kg）预处理可显著降低高剂量LNP 509或LNP 640引起的降压反应（分别为−23 ± 3和−26 ± 2 mmHg，与未预处理的家兔相比P < 0.05），而tertiapin-Q（10 μg/kg）本身不影响MAP。I1 R配体[125 I] LNP 911与PC 12细胞膜的最大特异性结合（Bmax）（296 ± 59 fmol/mg蛋白）通过氟吡汀预处理增强，而通过特硫平-Q预处理降低（分别为687 ± 122和68 ± 21 fmol/mg蛋白，与对照结合相比，P < 0.05）。结论GIRK通道的调节影响I1 R的功能，提示GIRK通道和I1 R可能是一个蛋白复合体。
Objective The present study examined the role of G-protein inwardly rectifying potassium (GIRK) channels in the depressor responses elicited by intracisternal injections of imidazoline-like drugs in anesthetized rabbits. Methods and results Intracisternal injections of the I1-imidazoline receptor (I1R) selective ligands LNP509 (30 μg/kg) and LNP640 (2 μg/kg) (subthreshold doses), and of the GIRK channel opener flupirtine (30 μg/kg) did not affect mean arterial blood pressure (MAP). LNP509 and LNP640, however, elicited substantial depressor responses in rabbits pretreated with flupirtine (−17 ± 2 and −18 ± 1 mmHg, respectively, P < 0.05). Injection of higher doses of LNP509 (200 μg/kg) or LNP640 (10 μg/kg) elicited substantial reductions in MAP (−45 ± 3 and −39 ± 2 mmHg, respectively, P < 0.05) in naive rabbits. The depressor responses elicited by the higher doses of LNP509 or LNP640 were markedly diminished by pretreatment with the GIRK channel blocker tertiapin-Q (10 μg/kg) (−23 ± 3 and −26 ± 2 mmHg, respectively, P < 0.05 compared with nonpretreated rabbits), whereas tertiapin-Q (10 μg/kg) did not affect MAP by itself. Maximal-specific binding (Bmax) of the I1R ligand [125I]LNP911 to PC12 cell membranes (296 ± 59 fmol/mg protein) was enhanced by flupirtine pretreatment whereas it was reduced by tertiapin-Q pretreatment (687 ± 122 and 68 ± 21 fmol/mg protein, respectively, P < 0.05 vs. control binding). Conclusion These findings demonstrate that the modulation of GIRK channels affects I1R's function and raise the possibility that GIRK channels, and I1Rs are parts of a single proteic complex.
I1-咪唑啉受体与 PC12 大鼠嗜铬细胞瘤细胞中甘油二酯积累的偶联。
DOI：
--
发表时间：
1996
期刊：
Molecular pharmacology.
影响因子：
--
作者：
Separovic,D;Kester,M;Ernsberger,P
通讯作者：
Ernsberger,P
DOI：
--
发表时间：
1984-07
期刊：
The Journal of pharmacology and experimental therapeutics
影响因子：
--
作者：
P. Bousquet;J. Feldman;J. Schwartz
通讯作者：
P. Bousquet;J. Feldman;J. Schwartz
人 I1-咪唑啉结合位点的配体结合亲和力与 α-2 肾上腺素受体亚型的高亲和力状态的比较。
DOI：
--
发表时间：
1996
期刊：
The Journal of pharmacology and experimental therapeutics.
影响因子：
--
作者：
Piletz,JE;Zhu,H;Chikkala,DN
通讯作者：
Chikkala,DN