McLean P G, Coupar I M
School of Pharmaceutical Biology and Pharmacology, Victorian College of Pharmacy, Monash University, Parkville, Victoria, Australia.
Eur J Pharmacol. 1996 Sep 26;312(2):215-25. doi: 10.1016/0014-2999(96)00456-6.
The 5-HT (5-hydroxytryptamine)-induced contractile biphasic concentration-effect curve in rat isolated jejunum was investigated. The pEC50 values for the first and second phases were 8.0 and 6.1, respectively. The responses were insensitive to atropine (0.1 microM), ketanserin (2 microM), (-)-pindolol (5 microM), yohimbine (0.1 microM) and GR 113808 ({1-[2-(methyl-sulphonylamino)ethyl]-4-piperidinyl}methyl 1-methyl-1 H-indole-3-carboxylate, 1 microM) but susceptible to cocaine (10 microM). The low affinity phase was blocked by tetrodotoxin (1 microM), ondansetron (1 microM) and SR48968 (S)-N-methyl-N-[4-(4-acetylamino-4-phenyl piperidino)-2-(3,4-dichlorophenyl)butyl]benzamide, 0.1 microM). The high affinity phase was antagonised non-surmountably by fluoxetine (1 microM) methysergide (0.1 microM), spiperone (0.1 microM) and methiothepin (0.1 microM). Ritanserin (0.01-0.1 microM) and mesulergine (0.01-0.1 microM) acted as surmountable, competitive antagonists with pA2 values of 8.0 and 8.1, respectively. Clozapine (0.1 microM) was a surmountable antagonist with an apparent pA2 value of 8.0. The rank potency order of the 5-HT receptor agonists was 5-CT (5-carboxyamidotryptamine) > or = 5-HT = 5-methoxytryptamine > or = alpha-methyl-5-HT > > 8-OH-DPAT ((+/-)-2-dipropyl-amino-8-hydroxy-1,2,3, 4-tetrahydronaphthalene) > dipropyl-5-CT > renzapride = sumatriptan. The responses to 5-HT and 5-CT were not potentiated by pargyline (10 and 100 microM). It is suggested that rat jejunum contains a neuronal 5-HT3 receptor facilitating neurokinin release and a contractile smooth muscle 5-HT receptor with a pharmacological operational profile similar to the cloned 5-ht7 receptor.
研究了5-羟色胺（5-HT）诱导的大鼠离体空肠收缩双相浓度-效应曲线。第一相和第二相的pEC50值分别为8.0和6.1。这些反应对阿托品（0.1微摩尔）、酮色林（2微摩尔）、（-）-吲哚洛尔（5微摩尔）、育亨宾（0.1微摩尔）和GR 113808（{1-[2-（甲基磺酰氨基）乙基]-4-哌啶基}甲基1-甲基-1H-吲哚-3-羧酸酯，1微摩尔）不敏感，但对可卡因（10微摩尔）敏感。低亲和力相被河豚毒素（1微摩尔）、昂丹司琼（1微摩尔）和SR48968（（S）-N-甲基-N-[4-（4-乙酰氨基-4-苯基哌啶基）-2-（3,4-二氯苯基）丁基]苯甲酰胺，0.1微摩尔）阻断。高亲和力相被氟西汀（1微摩尔）、美西麦角（0.1微摩尔）、螺哌隆（0.1微摩尔）和甲硫噻平（0.1微摩尔）不可逾越地拮抗。利坦色林（0.01 - 0.1微摩尔）和美舒麦角（0.01 - 0.1微摩尔）作为可逾越的竞争性拮抗剂，pA2值分别为8.0和8.1。氯氮平（0.1微摩尔）是一种可逾越的拮抗剂，表观pA2值为8.0。5-HT受体激动剂的效价顺序为5-羧基酰胺色胺（5-CT）≥5-HT = 5-甲氧基色胺≥α-甲基-5-HT＞＞（±）-2-二丙基氨基-8-羟基-1,2,3,4-四氢萘（8-OH-DPAT）＞二丙基-5-CT＞瑞扎曲普坦 = 舒马曲坦。对5-HT和5-CT的反应未被帕吉林（10和100微摩尔）增强。提示大鼠空肠含有促进神经激肽释放的神经元5-HT3受体和药理学作用特征类似于克隆的5-HT7受体的收缩性平滑肌5-HT受体。
