Involvement of central β2-adrenergic, NMDA and thromboxane A2 receptors in the pressor effect of anandamide in rats
Involvement of central β2-adrenergic, NMDA and thromboxane A2 receptors in the pressor effect of anandamide in rats
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DOI：
10.1007/s00210-010-0497-6
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发表时间：
2010-04-01
影响因子：
3.6
通讯作者：
Schlicker, E.
中科院分区：
文献类型：
--
作者：
Malinowska, B.;Zakrzeska, A.;Schlicker, E.
静脉注射（i. v.）注射内源性大麻素anandamide诱导三相心血管反应，包括通过未知的中枢和外周机制介导的升压效应。本研究的目的是确定负责对大麻素的升压反应的中枢机制。为此，研究了血栓素A（2）TP（舒洛曲班，达曲班，SQ 29548）、NMDA（MK-801）和β（2）-肾上腺素能受体（ICI 118551）拮抗剂对静脉注射和侧脑室注射（i. c. v.）在麻醉的大鼠中检查施用的大麻素。Anandamide（1.5-3 μ mol/kg，i.v.）或其稳定的类似物甲睾酮（methanandamide）（0.75A μ mol/kg，i. v.）血压升高25%大麻素（0.03 μ mol/动物i. c. v.）引起纯升压效应（20%），但仅在存在CB 1和TRPV 1受体拮抗剂的情况下。大麻素（i. v.或i. c. v.）通过静脉注射达曲班、舒洛曲班（各10 μ mol/kg）和/或SQ 29548（1 μ mol/kg）减少。SQ 29548（0.02 μ mol/动物i. c. v.）可降低anandamide i. v.的作用。和血栓素A（2）合成抑制剂furegrelate i. c. v.（每只动物1.8 μ mol）。ICI 118551、MK-801（各1 μ mol/kg i. v.）和双侧肾上腺切除术减弱了anandamide i. c. v.未能影响对大麻素（i. v.）花生四烯酸和甲基花生四烯酸不能与大鼠血小板的TP受体结合。本研究提示中枢β 2肾上腺素能受体、NMDA受体和血栓素A2受体参与了花生四烯酸诱导的肾上腺儿茶酚胺分泌及其升压作用。
Intravenous (i.v.) injection of the endocannabinoid anandamide induces triphasic cardiovascular responses, including a pressor effect mediated via unknown central and peripheral mechanism(s). The aim of the present study was to determine the central mechanism(s) responsible for the pressor response to anandamide. For this purpose, the influence of antagonists at thromboxane A(2) TP (sulotroban, daltroban, SQ 29548), NMDA (MK-801) and beta(2)-adrenergic receptors (ICI 118551) on the pressor effect induced by i.v. and intracerebroventricularly (i.c.v.) administered anandamide was examined in urethane-anaesthetized rats. Anandamide (1.5-3 A mu mol/kg, i.v.) or its stable analogue methanandamide (0.75 A mu mol/kg, i.v.) increased blood pressure by 25%. Anandamide (0.03 mu mol per animal i.c.v.) caused a pure pressor effect (by 20%) but only in the presence of antagonists of CB1 and TRPV1 receptors. The effects of cannabinoids (i.v. or i.c.v.) were diminished by i.v. daltroban, sulotroban (10 mu mol/kg each), and/or SQ 29548 (1 mu mol/kg). The effect of anandamide i.v. was reduced by SQ 29548 (0.02 mu mol per animal i.c.v.) and by the thromboxane A(2) synthesis inhibitor furegrelate i.c.v. (1.8 A mu mol per animal). ICI 118551, MK-801 (1 A mu mol/kg i.v. each), and bilateral adrenalectomy diminished the effect of anandamide i.c.v. Sulotroban (i.v.) failed to affect the response to anandamide (i.v.) in pithed rats, and anandamide and methanandamide did not bind to TP receptors in rat platelets. The present study suggests that central beta(2)-adrenergic, NMDA and thromboxane A(2) receptors are involved in the anandamide-induced adrenal secretion of catecholamines and their pressor effect in urethane-anaesthetized rats.