Yamano M, Miyata K
Neuroscienc Research Laboratories, Yamanouchi Pharmaceutical Co. Ltd., Tsukuba, Japan.
Eur J Pharmacol. 1996 Dec 19;317(2-3):353-9. doi: 10.1016/s0014-2999(96)00754-6.
We investigated the participation of cholinergic and tachykininergic mechanisms in 5-hydroxytryptamine (5-HT)-induced contraction via 5-HT3 receptors in longitudinal and circular muscle of guinea-pig isolated distal colon. 5-HT produced concentration-dependent contractile responses in longitudinal and circular muscle. The 5-HT3 receptor antagonists ramosetron (YM060) ((R)-5-[(1-methyl-3-indolyl) carbonyl]-4,5,6,7-tetrahydro-1H-benzimidazole hydrochloride), YM114 (KAE-393) ((R)-5-[(2,3-dihydro-1-indolyl)carbonyl]-4,5,6,7-tetrahydro-1 H-benzimidazole hydrochloride), ondansetron and granisetron produced a concentration-dependent shift to the right of the 5-HT concentration-response curves in both muscle. However, methysergide and GR113808 had no effect on 5-HT-induced contraction. In the longitudinal muscle, atropine concentration-dependently inhibited 5-HT-induced contraction, and tetrodotoxin abolished it. (+/-)-CP96,345 attenuated the contractile response to 5-HT, but (+/-)-SR48,968 had no effect on it. In the presence of atropine, (+/-)-CP96,345 completely blocked 5-HT-induced contraction. In the circular muscle, atropine had no effect on the contractile response to 5-HT, whereas tetrodotoxin completely suppressed it. The contractile response elicited by 5-HT in the circular muscle was not inhibited by either (+/-)-CP96,345, (+/-)-SR48,968, devazepide, L-365,260 or indomethacin. It is suggested that 5-HT acts via 5-HT3 receptors to release acetylcholine and substance P, which in turn are responsible for contraction of the longitudinal muscle. In the circular muscle, as in the longitudinal muscle, 5-HT-induced contraction is mediated by the 5-HT3 receptor. Unlike the case in longitudinal muscle, however, this contraction involves neither cholinergic nor tachykininergic transmission. It is also suggested that neither cholecystokinin (CCK) nor prostaglandins participate in 5-HT3 receptor-mediated contraction in circular muscle.
我们研究了胆碱能和速激肽能机制在5-羟色胺（5-HT）通过5-HT3受体诱导的豚鼠离体远端结肠纵肌和环肌收缩中的作用。5-HT在纵肌和环肌中产生浓度依赖性的收缩反应。5-HT3受体拮抗剂雷莫司琼（YM060）（（R）-5-[(1-甲基-3-吲哚基)羰基]-4,5,6,7-四氢-1H-苯并咪唑盐酸盐）、YM114（KAE-393）（（R）-5-[(2,3-二氢-1-吲哚基)羰基]-4,5,6,7-四氢-1H-苯并咪唑盐酸盐）、昂丹司琼和格拉司琼使两条肌肉中5-HT浓度-反应曲线浓度依赖性地右移。然而，麦角新碱和GR113808对5-HT诱导的收缩无影响。在纵肌中，阿托品浓度依赖性地抑制5-HT诱导的收缩，河豚毒素则使其消失。（±）-CP96,345减弱了对5-HT的收缩反应，但（±）-SR48,968对其无影响。在阿托品存在的情况下，（±）-CP96,345完全阻断了5-HT诱导的收缩。在环肌中，阿托品对5-HT的收缩反应无影响，而河豚毒素则完全抑制了该反应。5-HT在环肌中引发的收缩反应不受（±）-CP96,345、（±）-SR48,968、地伐西匹、L-365,260或吲哚美辛的抑制。提示5-HT通过5-HT3受体作用释放乙酰胆碱和P物质，进而导致纵肌收缩。在环肌中，与纵肌一样，5-HT诱导的收缩由5-HT3受体介导。然而，与纵肌不同的是，这种收缩既不涉及胆碱能传递也不涉及速激肽能传递。还提示胆囊收缩素（CCK）和前列腺素均不参与环肌中5-HT3受体介导的收缩。
