The ventral tegmental area as a putative target for tachykinins in cardiovascular regulation
The ventral tegmental area as a putative target for tachykinins in cardiovascular regulation
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DOI：
10.1038/sj.bjp.0706249
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发表时间：
2005-07-01
影响因子：
7.3
通讯作者：
Couture, R
中科院分区：
文献类型：
--
作者：
Deschamps, K;Couture, R
1在自由活动大鼠腹侧被盖区（VTA）微量注射速激肽受体激动剂和拮抗剂，研究三种速激肽受体在心血管调节中的相对参与。NK 1（[Sar（9），Met（O-2）（11）]SP）、NK 2（[beta-Ala（8）]NKA（4 - 10））和NK 3（senktide）受体的2种选择性激动剂（1 - 100 pmol）诱发血压、心率（HR）沿着行为表现（洗脸、嗅、抓头、直立、湿狗摇）的增加。在1 pmol时，NK 1和NK 3激动剂不影响行为和血压，但仅影响HR。3速激肽激动剂诱导的心血管反应可被预先注射NK 1受体拮抗剂选择性和可逆性阻断（LY 303870）（（R）-1-[N-（2-甲氧基苄基）乙酰氨基]3-（1H-吲哚-3-基）-2-[N-（2-（4-（哌啶-1-基）哌啶-1-基）乙酰基）氨基]丙烷），5 nmol），NK 2受体（SR 48968（[（S）-N-甲基-N-[4-乙酰氨基-4-苯基哌啶子基-2-基]）（3，4-二氯苯基）丁基]苯甲酰胺]），250 pmol）和NK 3受体（SB 235375（（-）-（S）-N-（α-乙基苄基）-3-（羧基甲氧基）2-苯基喹啉-4-甲酰胺），25 nmol）。除NK 2激动剂外，大多数行为效应也被拮抗剂阻断。4速激肽激动剂诱导的心血管反应被静脉内（i. v.）D-1多巴胺受体拮抗剂（SCH 23390，0.2 mg kg（-1））和β（1）-肾上腺素受体拮抗剂（阿替洛尔，5 mg kg（-1））治疗，但不包括D-2多巴胺受体拮抗剂（雷氯必利，0.16 mg kg（-1））。行为反应仅被SCH 23390阻断。5本研究首次提供了大鼠腹侧被盖区三种速激肽受体通过增加中脑多巴胺能传递影响血压和心率自主控制的药理学证据。这一机制可能参与协调行为和心血管对应激和伤害性刺激的反应。
1 Tachykinin receptor agonists and antagonists were microinjected into the ventral tegmental area (VTA) to study the relative participation of the three tachykinin receptors in cardiovascular regulation in freely behaving rat. 2 Selective agonists (1 - 100 pmol) for NK1 ([Sar(9), Met (O-2)(11)]SP), NK2 ([beta-Ala(8)]NKA (4 - 10)) and NK3 ( senktide) receptors evoked increases in blood pressure, heart rate (HR) along with behavioural manifestations ( face washing, sniffing, head scratching, rearing, wet dog shake). At 1 pmol, NK1 and NK3 agonists did not affect behaviour and blood pressure but only HR. 3 Tachykinin agonists-induced cardiovascular responses were selectively and reversibly blocked by the prior injection of antagonists for NK1 receptors (LY 303870 ((R)-1-[N-(2-methoxybenzyl)acetylamino]3-(1H-indol-3-yl)-2-[N-(2-(4-(piperidin-1-yl)piperidin-1-yl) acetyl) amino] propane), 5 nmol), NK2 receptors (SR 48968 ([(S)-N-methyl-N-[4-acetylamino-4-phenylpiperidino-2-(3,4-dichlorophenyl)butyl] benzamide]), 250 pmol) and NK3 receptors (SB 235375 ((-)-(S)-N-(alpha-ethylbenzyl)-3-(carboxymethoxy)2-phenylquinoline-4-carboxamide), 25 nmol). With the exception of the NK2 agonist, most behavioural effects were also blocked by antagonists. 4 Tachykinin agonists-induced cardiovascular responses were inhibited by intravenous (i.v.) treatments with antagonists for D-1 dopamine receptor (SCH23390, 0.2 mg kg (-1)) and beta(1)-adrenoceptor (atenolol, 5mg kg(-1)) but not for D-2 dopamine receptor (raclopride, 0.16 mgkg(-1)). Behavioural responses were blocked by SCH23390 only. 5 The present study provides the first pharmacological evidence that the three tachykinin receptors in the rat VTA can affect the autonomic control of blood pressure and HR by increasing midbrain dopaminergic transmission. This mechanism may be involved in the coordination of behavioural and cardiovascular responses to stress and noxious stimulation.