Shenker A, Maayani S, Weinstein H, Green J P
Mol Pharmacol. 1987 Apr;31(4):357-67.
Two 5-hydroxytryptamine (5-HT) receptors mediate stimulation of adenylate cyclase activity in membranes of adult guinea pig hippocampus. The two receptors were characterized with agonists and antagonists and with the aid of computerized curve-fitting procedures. Each receptor mediates about 50% of the maximal response to 5-HT. 5-HT is about 10-fold more potent in eliciting response through one cyclase-linked receptor (RH) than the other (RL). The concentrations of 5-HT that elicit half-maximal response through RH and RL are 43 +/- 6 nM and 414 +/- 53 nM, respectively. 5-Methoxytryptamine (5-MeOT) and 5-HT are approximately equipotent at each receptor. The agonists tryptamine and bufotenine are less potent than 5-HT at both receptors, and each is about 50-fold selective for RH. The two receptors are best discriminated by the agonists 5-carboxamidotryptamine (5-CONH2-T) and 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), both of which are selective for RH. 5-CONH2-T is about 7-fold more potent than 5-HT at RH. The rank order of agonist potencies at RH (5-CONH2-T greater than 8-OH-DPAT = 5-HT = 5-MeOT greater than bufotenine greater than tryptamine) differs from that at RL (5-HT = 5-MeOT greater than bufotenine greater than tryptamine = 5-CONH2-T greater than 8-OH-DPAT). Spiperone acts as a simple competitive antagonist at RH, with a dissociation constant of 20 nM, but it is at least 100-fold less potent as an antagonist at RL. The relatively low affinities of the selective 5-HT antagonists ketanserin and MDL 72222 for RH and RL indicate that neither receptor may be classified as the 5-HT2 or as the 5-HT3 (i.e., peripheral neuronal) type. The characteristics of RH suggest that it is a functional correlate of the 5-HT1A-binding site in brain. RL appears not to correspond to a known 5-HT-binding site, but it may be homologous to receptors that mediate 5-HT-stimulated adenylate cyclase activity in other systems such as infant rat colliculi. RH and RL may also mediate stimulation of adenylate cyclase activity by 5-HT in hippocampal membranes of adult rat.
两种5-羟色胺（5-HT）受体介导成年豚鼠海马体膜中腺苷酸环化酶活性的刺激。借助激动剂和拮抗剂，并通过计算机曲线拟合程序对这两种受体进行了表征。每种受体介导对5-HT最大反应的约50%。5-HT通过一种与环化酶相连的受体（RH）引发反应的效力比另一种受体（RL）高约10倍。通过RH和RL引发半数最大反应的5-HT浓度分别为43±6 nM和414±53 nM。5-甲氧基色胺（5-MeOT）和5-HT在每种受体上的效力大致相当。激动剂色胺和蟾蜍色胺在两种受体上的效力均低于5-HT，且它们对RH的选择性均约为50倍。两种受体通过激动剂5-羧酰胺色胺（5-CONH2-T）和8-羟基-2-（二正丙基氨基）四氢萘（8-OH-DPAT）能得到最佳区分，这两种激动剂对RH均具有选择性。5-CONH2-T在RH上的效力比5-HT高约7倍。RH上激动剂效力顺序（5-CONH2-T＞8-OH-DPAT = 5-HT = 5-MeOT＞蟾蜍色胺＞色胺）与RL上的顺序（5-HT = 5-MeOT＞蟾蜍色胺＞色胺 = 5-CONH2-T＞8-OH-DPAT）不同。螺哌隆在RH上作为简单竞争性拮抗剂起作用，解离常数为20 nM，但它作为RL上的拮抗剂效力至少低100倍。选择性5-HT拮抗剂酮色林和MDL 72222对RH和RL的亲和力相对较低，这表明这两种受体均不能归类为5-HT2或5-HT3（即外周神经元）类型。RH的特性表明它是脑中5-HT1A结合位点在功能上相对应的部分。RL似乎与已知的5-HT结合位点不对应，但它可能与介导其他系统（如幼鼠小丘）中5-HT刺激的腺苷酸环化酶活性的受体同源。RH和RL也可能介导成年大鼠海马体膜中5-HT对腺苷酸环化酶活性的刺激。
