Clineschmidt B V, Reiss D R, Pettibone D J, Robinson J L
J Pharmacol Exp Ther. 1985 Dec;235(3):696-708.
1-Arylpiperazines (MK-212, quipazine, m-chlorophenylpiperazine and m-trifluoromethylphenylpiperazine) caused a serotonin (5-HT) receptor-mediated contraction of rat fundic strips. m-chlorophenylpiperazine and m-trifluoromethylphenylpiperazine had high affinity for the receptor but little efficacy, whereas quipazine and MK-212 had lesser affinity and much greater efficacy. 5-HT itself was the most potent (EC50 = 6-9 nM) agonist and possessed the greatest affinity (KA = 9.7 nM). Assessment of receptor occupancy vs. functional response (as well as receptor alkylation studies) demonstrated a very small, if any, receptor reserve in this tissue. Several arylquinolizines were found to be competitive antagonists of 5-HT-induced contraction, the most potent being L-653,267 and rauwolscine (KB values = 1.9 and 3.8 nM). Clozapine, trazodone and propranolol were identified as less potent, competitive antagonists, whereas various ergolines (including LY 53857), L-646,462 (cyproheptadine analog) and mianserin were noncompetitive. Potent 5-HT2 receptor antagonists (pirenpirone and ketanserin) antagonized only weakly or were without effect against 5-HT, indicating that the fundic 5-HT receptor is not of the 5-HT2 subtype. Because the fundic receptor has high affinity for 5-HT (as does the 5-HT1 binding site in brain tissue), the possible correspondence of the fundic 5-HT receptor with the 5-HT1 recognition site in rat brain cortex was considered. 5-HT, the nonindole agonists (1-arylpiperazines) and the competitive antagonists all competed with [3H]-5-HT for the 5-HT1 site. However, all compounds except 5-HT had Hill slopes significantly less than 1.0, precluding a valid comparison with dissociation constants derived pharmacologically in the fundus. With respect to having a high affinity for 5-HT, the 5-HT receptor mediating contraction of fundic smooth muscle resembles the 5-HT1 recognition site (as defined in brain tissue by radioligand binding), but identity remains unproven.
1-芳基哌嗪类化合物（MK-212、喹哌嗪、间氯苯基哌嗪和间三氟甲基苯基哌嗪）可引起大鼠胃底肌条由5-羟色胺（5-HT）受体介导的收缩。间氯苯基哌嗪和间三氟甲基苯基哌嗪对该受体具有高亲和力但效能较低，而喹哌嗪和MK-212的亲和力较低但效能高得多。5-HT本身是最有效的激动剂（半数有效浓度EC50 = 6 - 9 nM），且具有最大的亲和力（亲和常数KA = 9.7 nM）。受体占有率与功能反应的评估（以及受体烷基化研究）表明，在该组织中即使存在受体储备也非常少。发现几种芳基喹啉嗪是5-HT诱导收缩的竞争性拮抗剂，其中最有效的是L-653,267和萝芙辛（解离常数KB值分别为1.9和3.8 nM）。氯氮平、曲唑酮和普萘洛尔被确定为效力较弱的竞争性拮抗剂，而各种麦角碱类化合物（包括LY 53857）、L-646,462（赛庚啶类似物）和米安色林是非竞争性的。强效5-HT2受体拮抗剂（哌仑西平和酮色林）对5-HT的拮抗作用微弱或无作用，表明胃底5-HT受体不是5-HT2亚型。由于胃底受体对5-HT具有高亲和力（与脑组织中的5-HT1结合位点一样），因此考虑了胃底5-HT受体与大鼠脑皮质中5-HT1识别位点可能的对应关系。5-HT、非吲哚类激动剂（1-芳基哌嗪类化合物）和竞争性拮抗剂均与[3H]-5-HT竞争5-HT1位点。然而，除5-HT外的所有化合物的希尔斜率均显著小于1.0，这使得无法与从胃底药理学推导的解离常数进行有效比较。就对5-HT具有高亲和力而言，介导胃底平滑肌收缩的5-HT受体类似于5-HT1识别位点（如通过放射性配体结合在脑组织中所定义的），但尚未证实二者相同。
