5-羟色胺诱导的兔大脑中动脉和大脑后动脉收缩中5-HT1D受体的介导作用。

Mediation by 5-HT1D receptors of 5-hydroxytryptamine-induced contractions of rabbit middle and posterior cerebral arteries.

作者信息

Deckert V, Pruneau D, Elghozi J L

机构信息

Laboratoires Fournier, Daix, France.

出版信息

Br J Pharmacol. 1994 Jul;112(3):939-45. doi: 10.1111/j.1476-5381.1994.tb13171.x.

DOI:10.1111/j.1476-5381.1994.tb13171.x

PMID:7921624

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1910179/

Abstract

5-Hydroxytryptamine (5-HT) receptor-mediated contraction of endothelium denuded rabbit middle (MCA) and posterior (PCA) cerebral arteries was characterized by use of selective agonists and antagonists for different 5-HT receptor subtypes. 2. 5-HT and various 5-HT receptor agonists contracted the arteries with the following rank order of potency in MCA: 5-carboxamidotryptamine (5-CT) > 5-HT > 5-methoxytryptamine (5-MeOT) > sumatriptan > alpha-methyl-5-HT (alpha-Me-5-HT) >> 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) and in PCA: 5-CT > 5-HT > sumatriptan > 5-MeOT > alpha-Me-5-HT >> 8-OH-DPAT. With few exceptions, the maximal contractile responses of these agonists were similar to that induced by 5-HT. 3. The selective antagonists of 5-HT2A/2C (ketanserin), 5-HT4 (SDZ 205-557) and 5-HT1A/1B (S-(-)-propranolol) sites were devoid of inhibitory effect on 5-HT-mediated contraction in both MCA and PCA, thus excluding activation of the corresponding receptors. 4. In both arteries, the contraction-response curve to 5-HT was unaffected by the 5-HT3 receptor antagonist, ICS 205-930 (0.01 and 0.1 microM) whilst a small (3 and 6 fold displacement) was seen with MDL 72222 (0.1 and 1 microM). 5. The mixed 5-HT1-like/5-HT2A receptor antagonist, methiothepin (0.001-0.1 microM), was a potent antagonist of 5-HT-induced contractions in both arteries, giving pA2 values of 9.4 +/- 0.7 and 9.6 +/- 0.8 in MCA and PCA, respectively. 6. Rauwolscine (O.1-10 MicroM) and yohimbine (0.3, 3 MicroM) inhibited contractions to 5-HT in a competitive manner, pA2 values of 7.1 +/- 0.6 and 6.7 +/-0.6 were determined for rauwolscine in MCA and PCA,respectively. An apparent pA2 value of 6.9 +/-0.2 was calculated for yohimbine (3 MicroM) in both MCA and PCA.7. In conclusion, these results suggest that the contractile response to 5-HT in rabbit isolated MCA and PCA is predominantly mediated by the 5-HTID receptor subtype, although a small contribution by 5-HT3 receptors cannot be excluded.

摘要

通过使用针对不同5-羟色胺（5-HT）受体亚型的选择性激动剂和拮抗剂，对内皮剥脱的兔大脑中动脉（MCA）和大脑后动脉（PCA）中5-HT受体介导的收缩特性进行了研究。2. 5-HT和各种5-HT受体激动剂使动脉收缩，在MCA中其效力顺序如下：5-羧基色胺（5-CT）>5-HT>5-甲氧基色胺（5-MeOT）>舒马曲坦>α-甲基-5-HT（α-Me-5-HT）>>8-羟基-2-（二正丙基氨基）四氢萘（8-OH-DPAT），在PCA中：5-CT>5-HT>舒马曲坦>5-MeOT>α-Me-5-HT>>8-OH-DPAT。除少数例外，这些激动剂的最大收缩反应与5-HT诱导的相似。3. 5-HT2A/2C（酮色林）、5-HT4（SDZ 205-557）和5-HT1A/1B（S-（-）-普萘洛尔）位点的选择性拮抗剂对MCA和PCA中5-HT介导的收缩均无抑制作用，因此排除了相应受体的激活。4. 在两条动脉中，5-HT3受体拮抗剂ICS 205-930（0.01和0.1微摩尔）对5-HT的收缩反应曲线无影响，而MDL 72222（0.1和1微摩尔）则使曲线有小幅度（3倍和6倍位移）变化。5. 5-HT1样/5-HT2A受体混合拮抗剂美噻吨（0.001 - 0.1微摩尔）是两条动脉中5-HT诱导收缩的强效拮抗剂，在MCA和PCA中的pA2值分别为9.4±0.7和9.6±0.8。6. 利血平（0.1 - 10微摩尔）和育亨宾（0.3、3微摩尔）以竞争性方式抑制对5-HT的收缩，利血平在MCA和PCA中的pA2值分别测定为7.1±0.6和6.7±0.6。育亨宾（3微摩尔）在MCA和PCA中的表观pA2值计算为6.9±0.2。7. 总之，这些结果表明，兔离体MCA和PCA中对5-HT的收缩反应主要由5-HTID受体亚型介导，尽管不能排除5-HT3受体有小的作用。