Harris Lydia C, Awe S Olubusayo, Opere Catherine A, LeDay Angela M, Ohia Sunny E, Sharif Najam A
Department of Pharmacy Sciences, School of Pharmacy and Allied Health Professions, Creighton University, Omaha, NE 68178, USA.
J Ocul Pharmacol Ther. 2002 Aug;18(4):339-48. doi: 10.1089/10807680260218506.
The pharmacology of prejunctional serotonin (5-HT) heteroreceptors that regulate the release of norepinephrine (NE) was studied in isolated bovine and human iris-ciliary bodies. The effect of exogenous 5-HT and various 5-HT receptor agonists was examined on the release of [3H]-norepinephrine ([3H]NE). Both 5-HT and m-chlorophenyl-biguanide (m-CPBG) caused enhancement in the field-stimulated release of [3H]NE from bovine tissues whereas 5-carboxamidotryptamine (5-CT) had no such effect. On the other hand, 8hydroxy-dipropylaminotetralin (8-OH-DPAT), caused a significant dose-related inhibition of evoked [3H]NE release. In human iris-ciliary bodies, 5-HT caused an inhibitory response on electrically-evoked [3H]NE release at low concentrations but produced an excitatory action at concentrations greater than 3 microM. To further confirm the nature of the prejunctional 5-HT heteroreceptors regulating [3H]NE release, effects of 5-HT3, 5-HT6 and 5-HT7 receptor antagonists were examined on a standard response to 5-HT. All antagonists examined caused a concentration-dependent inhibition of the response elicited by the standard 5-HT-induced response with the following rank order of potency (as measured by IC30 values): MDL-72222 >> SB-258719 > RO-04-690. We conclude that the excitatory prejunctional 5-HT heteroreceptors present in bovine iris-ciliary bodies belong to the 5-HT3 receptor subtype.
在离体牛和人虹膜睫状体中研究了调节去甲肾上腺素(NE)释放的突触前5-羟色胺(5-HT)异受体的药理学。检测了外源性5-HT和各种5-HT受体激动剂对[3H]-去甲肾上腺素([3H]NE)释放的影响。5-HT和间氯苯基双胍(m-CPBG)均可增强牛组织中电场刺激引起的[3H]NE释放,而5-羧基色胺(5-CT)则无此作用。另一方面,8-羟基二丙基氨基四氢萘(8-OH-DPAT)可引起剂量依赖性的显著抑制诱发的[3H]NE释放。在人虹膜睫状体中,5-HT在低浓度时对电诱发的[3H]NE释放产生抑制反应,但在浓度大于3μM时产生兴奋作用。为了进一步证实调节[3H]NE释放的突触前5-HT异受体的性质,检测了5-HT3、5-HT6和5-HT7受体拮抗剂对5-HT标准反应的影响。所有检测的拮抗剂均对标准5-HT诱导反应引发的反应产生浓度依赖性抑制,其效力顺序如下(以IC30值衡量):MDL-72222 >> SB-258719 > RO-04-690。我们得出结论,牛虹膜睫状体中存在的兴奋性突触前5-HT异受体属于5-HT3受体亚型。