Roles of 5-hydroxytryptamine (5-HT) receptor subtypes in the inhibitory effects of 5-HT on C-fiber responses of spinal wide dynamic range neurons in rats
Roles of 5-hydroxytryptamine (5-HT) receptor subtypes in the inhibitory effects of 5-HT on C-fiber responses of spinal wide dynamic range neurons in rats
复制标题
5-羟色胺（5-HT）受体亚型在 5-HT 对大鼠脊髓宽动态范围神经元 C 纤维反应的抑制作用中的作用
DOI：
10.1124/jpet.106.115204
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发表时间：
2007-06-01
影响因子：
3.5
通讯作者：
Wan, You
中科院分区：
文献类型：
--
作者：
Liu, Feng-Yu;Xing, Guo-Gang;Wan, You
5-羟色胺（5-HT； 5-羟色胺）在伤害感觉的下行控制中起重要作用。5-羟色胺及其受体在脊髓水平的伤害性传递调节中已被广泛研究，使用行为测试可能受5-羟色胺对运动表现和皮肤温度的影响。本研究采用电生理方法，系统研究了5-HT受体亚型在大鼠脊髓宽动态范围神经元（WDR）对c -纤维输入的抑制作用中的作用。在基础条件下，脊髓外用5-羟色胺可剂量依赖性地抑制WDR神经元的c -纤维反应，而5-HT1A [WAY 100635] [N-[2-[4（2-甲氧基苯基）-1-哌嗪基]乙基]-N-2-吡啶基-环己胺甲酸盐]]，5-HT1B [GR 55562][3-[3-（二甲氨基）丙基]-4-羟基-N-[4-（4-吡啶基）苯基]苯甲酰胺二盐酸]]，5-HT2A[酮色林][3-[2-[4-（氟苯甲酰）-1-哌嗪基]乙基]-2,4[1H]，5- ht2c [RS 102221][8-[5-(2,4-二甲氧基-5-（4-三氟甲基苯基磺胺）苯基-5-氧戊基]-1,3,8-三氮唑斯皮罗[4.5]癸烷-2,4-二酮盐酸盐]]，5- ht3 [MDL 72222] [3-tropanyl-3,5二氯苯甲酸酯]]，5- ht4 [GR 113808([1-[2-[（甲基磺酰基）氨基]乙基]-4-哌啶基]甲基1-甲基- 1h -吲哚-3-羧酸盐]]对其本身没有影响。5-HT的抑制作用可被5- ht1b （GR 55562）、5- ht2a（酮色林）、5- ht2c （RS 102221）、5- ht3 （MDL 72222）和5- ht4 （GR 113808）拮抗剂逆转，但5- ht1a （WAY 100635）受体拮抗剂不能逆转。局部受体激动剂管理5-HT1A [(2 r) - (+) 8-hydroxy-2 (di-n-propylamino)萘满氢溴酸盐),5-HT1B [CGS 12066 [7-trifluoromethyl-4 - (4-methyl-1-piperazinyl) pyrrolo [1, 2 - a]喹喔啉马来酸盐]],5-HT2A(马来酸alpha-methyl-5-hydroxytryptamine) 5-HT2C[可212 [6-chloro-2 - (1 - piperazinyl)吡嗪盐酸]],5-HT3 [1 - (3-chlorophenyl)双胍盐酸盐],和5-HT4[2 -(1 -(4 -增效)piperazinyl]苯并噻唑)也抑制了C-responses。这些结果表明，在基础条件下，5-羟色胺对背角神经元的c -反应不存在强直性抑制作用，多种5-HT受体亚型包括1B、2A、2C、3和4可能参与了5-HT的抑制作用。
5-Hydroxytryptamine ( 5-HT; serotonin) plays an important role in the descending control of nociception. 5-HT and its receptors have been extensively studied in the modulation of nociceptive transmission at the spinal level using behavioral tests that may be affected by the effects of 5-HT on motor performance and skin temperature. Using electrophysiological methods, the present study aimed to systematically investigate the roles of 5-HT receptor subtypes on the inhibitory effects of 5-HT on responses of the spinal wide dynamic range ( WDR) neurons to C-fiber inputs in rats. Under basal conditions, topical application of 5-HT to the spinal cord inhibited the C-fiber responses of WDR neurons dose-dependently, whereas antagonists of 5-HT1A [ WAY 100635 [ N-[ 2-[ 4( 2-methoxyphenyl)-1-piperazinyl] ethyl]-N-2-pyridinyl-cyclohexanecarboxamide maleate salt]], 5-HT1B [GR 55562 [ 3-[ 3-( dimethylamino) propyl]-4-hydroxy-N-[ 4-(4- pyrid-dinyl) phenyl] benzamide dihydrochloride]], 5-HT2A [ ketanserin [ 3-[ 2-[ 4-( fluorobenzoyl)-1-piperidinyl] ethyl]-2,4[ 1H, 3H]-quinazolinedione tartrate]], 5-HT2C [ RS 102221 [ 8-[ 5-( 2,4-dimethoxy-5-(4-trifluoromethylphenylsulfonamido) phenyl-5-oxopentyl]-1,3,8-triazaspiro[ 4.5] decane-2,4-dione hydrochloride]], 5-HT3 [ MDL 72222 [ 3-tropanyl-3,5dichlorobenzoate]], and 5-HT4 [ GR 113808 ([ 1-[ 2-[( methylsulfonyl)amino] ethyl]-4-piperidinyl] methyl 1-methyl-1H-indole-3-carboxylate)] had no effect on their own. The inhibitory effects of 5- HT were reversed by antagonists of 5-HT1B ( GR 55562), 5-HT2A ( ketanserin), 5-HT2C ( RS 102221), 5-HT3 ( MDL 72222), and 5-HT4 ( GR 113808) but not by 5-HT1A ( WAY 100635) receptor antagonists. Topical administration of agonists of 5-HT1A [( 2R)-( +)-8-hydroxy-2-(di-n-propylamino) tetralin hydrobromide], 5-HT1B [ CGS 12066 [ 7-trifluoromethyl-4-( 4-methyl-1-piperazinyl) pyrrolo[ 1,2- a] quinoxaline maleate salt]], 5-HT2A ( alpha-methyl-5-hydroxytryptamine maleate), 5-HT2C [ MK 212 [ 6-chloro-2-( 1- piperazinyl) pyrazine hydrochloride]], 5-HT3 [ 1-( 3-chlorophenyl) biguanide hydrochloride], and 5-HT4 [ 2-[ 1-( 4- piperonyl) piperazinyl] benzothiazole] also inhibited the C-responses. These results suggest that, under basal conditions, there is no tonic serotonergic inhibition on the C-responses of dorsal horn neurons, and multiple 5-HT receptor subtypes including 1B, 2A, 2C, 3, and 4 may be involved in mediating the inhibitory effects of 5- HT.