Institute of Pharmaceutical Innovation, Bradford, UK.
Pharmacology. 2011;88(3-4):225-32. doi: 10.1159/000331878. Epub 2011 Oct 12.
The relevance of age on serotonergic involvement in the control of alimentary contractility has not been pharmacologically described. Experiments were performed to investigate the effects of acetylcholine, atropine, 5-hydroxytryptamine (5-HT) and its related drugs on intestinal segments taken from the neonatal and adult ileum. 5-HT induced concentration-dependent contractions of ileum irrespective of age; however, these contractions were diminished by pretreatment with atropine only in neonatal tissues. In tissues taken from both the neonatal and adult ileum, methysergide (5-HT(1/2/5-7) receptor antagonist), ritanserin (5-HT(2) receptor antagonist), and RS23597-190/SB204070 (5-HT(4) receptor antagonists) all differentially reduced 5-HT-induced contractions at a concentration <100 μmol/l. At higher concentrations, the contractions were comparable to those in control tissues. Granisetron and ondansetron (5-HT(3) receptor antagonists) significantly reduced contractions induced by 5-HT at concentrations >30 μmol/l in both neonatal and adult ileum. Combined treatments with ritanserin, granisetron, plus RS23597-190 reduced or abolished contraction responses induced in neonatal ileum by 5-HT. SB269970A (5-HT(7) receptor antagonist) and WAY100635 (5-HT(1A) receptor antagonist) failed to influence contractile responses induced by 5-HT or 5-HT receptor agonists. Pretreatments with WAY100635 and SB267790A also had no influence on the contractile responses induced by 5-HT(1A/7) receptor agonist, 5-CT, and 5-HT(1A) receptor agonist, 8-OH-DPAT, which itself failed to induce a measurable response. It is concluded that the 5-HT-induced contractions in segments taken from both the neonatal and adult rat ileum were mediated via 5-HT(2) receptors, 5-HT(3) receptors and 5-HT(4) receptors. However, the effect of atropine on the neonatal rat intestine indicates that the mechanism of serotonergic involvement in ileal contractility is influenced by age.
年龄对 5-羟色胺能系统参与控制摄食活动的相关性尚未进行药理学描述。实验目的是研究乙酰胆碱、阿托品、5-羟色胺（5-HT）及其相关药物对新生和成年回肠段的影响。5-HT 诱导的回肠收缩具有浓度依赖性，与年龄无关；然而，只有在新生组织中，预先用阿托品处理才能减少这些收缩。在来自新生和成年回肠的组织中，麦角酰二乙胺（5-HT1/2/5-7 受体拮抗剂）、利坦色林（5-HT2 受体拮抗剂）和 RS23597-190/SB204070（5-HT4 受体拮抗剂）均以浓度 <100μmol/L 差异降低 5-HT 诱导的收缩。在更高的浓度下，收缩与对照组织相当。格拉司琼和昂丹司琼（5-HT3 受体拮抗剂）在新生和成年回肠中均显著降低 5-HT 诱导的收缩，浓度>30μmol/L。利坦色林、格拉司琼和 RS23597-190 的联合处理降低或消除了 5-HT 在新生回肠中诱导的收缩反应。SB269970A（5-HT7 受体拮抗剂）和 WAY100635（5-HT1A 受体拮抗剂）未能影响 5-HT 或 5-HT 受体激动剂诱导的收缩反应。WAY100635 和 SB267790A 的预处理也没有影响 5-HT1A/7 受体激动剂 5-CT 和 5-HT1A 受体激动剂 8-OH-DPAT 诱导的收缩反应，而后者本身未能诱导可测量的反应。结论是，来自新生和成年大鼠回肠段的 5-HT 诱导收缩是通过 5-HT2 受体、5-HT3 受体和 5-HT4 受体介导的。然而，阿托品对新生大鼠肠道的作用表明，5-羟色胺能系统参与回肠收缩的机制受年龄影响。
