血清素引发成年大鼠海马膜中腺苷酸环化酶活性的放大。

Serotonin-elicited amplification of adenylate cyclase activity in hippocampal membranes from adult rat.

作者信息

Barbaccia M L, Brunello N, Chuang D M, Costa E

出版信息

J Neurochem. 1983 Jun;40(6):1671-9. doi: 10.1111/j.1471-4159.1983.tb08141.x.

DOI:10.1111/j.1471-4159.1983.tb08141.x

Abstract

The activity of the adenylate cyclase located in membranes prepared from hippocampus of adult rat can be stimulated by serotonin (5-HT) (Ka = 4 X 10(-7) M). The maximal effect is obtained with 10 microM 5-HT. Freezing of the tissue decreases the 5-HT stimulation; this stimulation is optimal in the presence of 82.5 mM Tris-maleate buffer (pH 7.4) and 50 microM GTP. The adenylate cyclase activity of membranes prepared from cortex, hypothalamus, and colliculi of adult rats is not significantly stimulated by 5-HT. Dopamine (DA) also stimulates adenylate cyclase located in hippocampal membranes; its effect can be blocked by haloperidol (10(-6) M), which fails to inhibit 5-HT stimulation. Moreover, p-chlorophenylalanine treatment for 2 weeks or selective lesion of 5-HT axons afferent to the hippocampus increases the Vmax of 5-HT stimulation, but fails to change that of DA stimulation. The 5-HT stimulation can be inhibited by metergoline, spiroperidol, and pizotyline (10(-6) M), but not by the same concentrations of mianserin, ketanserine, alprenolol, phenoxybenzamine, and mepyramine. The 5-HT stimulation of adenylate cyclase of hippocampal membranes can be mimicked by tryptamine, 5-methoxytryptamine, bufotenine, and to a lesser extent by LSD; N-methyltryptamine, N-methyltryptophan, and 5-hydroxytryptophan are inactive. Studies with kainic acid suggest that the 5-HT recognition site (5-HT1) linked to adenylate cyclase is located on the membrane of intrinsic hippocampal neurons.

摘要

成年大鼠海马制备的膜中腺苷酸环化酶的活性可被血清素（5-羟色胺，5-HT）刺激（解离常数Ka = 4×10⁻⁷ M）。10微摩尔5-HT可产生最大效应。组织冷冻会降低5-HT刺激；在82.5毫摩尔三羟甲基氨基甲烷-马来酸缓冲液（pH 7.4）和50微摩尔鸟苷三磷酸（GTP）存在时，这种刺激最为理想。成年大鼠皮质、下丘脑和小脑中制备的膜的腺苷酸环化酶活性未被5-HT显著刺激。多巴胺（DA）也刺激海马膜中的腺苷酸环化酶；其作用可被氟哌啶醇（10⁻⁶ M）阻断，而氟哌啶醇不能抑制5-HT刺激。此外，用对氯苯丙氨酸处理2周或选择性损伤传入海马的5-HT轴突会增加5-HT刺激的最大反应速度（Vmax），但不会改变DA刺激的Vmax。5-HT刺激可被麦角苄酯、螺哌啶醇和匹唑替林（10⁻⁶ M）抑制，但相同浓度的米安色林、酮色林、阿普洛尔、苯氧苄胺和甲氧苄二胺则不能。海马膜腺苷酸环化酶的5-HT刺激可被色胺、5-甲氧基色胺、蟾蜍色胺模拟，麦角酸二乙胺在较小程度上也可模拟；N-甲基色胺、N-甲基色氨酸和5-羟色氨酸无活性。用 kainic 酸进行的研究表明，与腺苷酸环化酶相连的5-HT识别位点（5-HT1）位于海马固有神经元的膜上。