BROMOCRIPTINE, A DOPAMINE D2 RECEPTOR AGONIST, INHIBITS ADENYLYL-CYCLASE ACTIVITY IN RAT OLFACTORY EPITHELIUM
BROMOCRIPTINE, A DOPAMINE D2 RECEPTOR AGONIST, INHIBITS ADENYLYL-CYCLASE ACTIVITY IN RAT OLFACTORY EPITHELIUM
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DOI：
10.1016/0306-4522(93)90119-z
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发表时间：
1993-11-01
期刊：
影响因子：
3.3
通讯作者：
BRUCH, RC
中科院分区：
文献类型：
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作者：
MANIAFARNELL, BL;FARBMAN, AI;BRUCH, RC
嗅球中存在大量多巴胺能神经元，表明多巴胺在嗅觉中起着重要作用。多巴胺D2受体在嗅觉感觉神经元中产生[Shipley等（1991）Chem. Senses 16，5]，并且在嗅球的神经和肾小球层中的它们的末端中以相对高的浓度发现[Nickell等（1991）NeuroReport 2，9-12]。在其他系统中，D2受体通过抑制性G蛋白与腺苷酸环化酶连接，受体的激活导致酶的抑制。我们研究了大鼠嗅粘膜，以确定是否D2受体的功能连接到腺苷酸环化酶，因为他们在其他组织。腺苷酸环化酶存在于感觉上皮的嗅纤毛和嗅球的嗅神经末梢中。溴隐亭，一种D2受体激动剂，被添加到正常和单侧延髓切除成年大鼠的嗅上皮膜制剂和制剂进行测定毛喉素刺激腺苷酸环化酶活性。在未手术的动物溴隐亭显着抑制腺苷酸环化酶的活性，并取消百日咳毒素治疗后的抑制。在粘膜从单侧延髓切除动物，我们看到了显着降低腺苷酸环化酶活性的操作侧和进一步减少，在响应溴隐亭。数据表明，溴隐亭降低腺苷酸环化酶活性的嗅觉组织，特别是在感觉神经元，和反应是依赖于百日咳毒素敏感的G-蛋白。由于没有多巴胺能输入到嗅上皮，我们建议多巴胺D2受体更可能在功能上连接到腺苷酸环化酶，被运输到轴突末端比纤毛中的腺苷酸环化酶。结果还表明，受体在被转运到神经末梢之前与G蛋白偶联。
The presence of large numbers of dopaminergic neurons in the olfactory bulb suggests that dopamine plays an important role in olfaction. Dopamine D2 receptors are produced in olfactory sensory neurons [Shipley et al. (1991) Chem. Senses 16, 5] and found in relatively high concentrations in their terminals in the nerve and glomerular layers of the olfactory bulb [Nickell et al. (1991) NeuroReport 2, 9-12]. In other systems D2 receptors are linked to adenylyl cyclase by an inhibitory G-protein, and activation of the receptors results in inhibition of the enzyme. We examined rat olfactory mucous membrane to determine whether the D2 receptors were linked functionally to adenylyl cyclase as they are in other tissues. Adenylyl cyclase is found in both the olfactory cilia of the sensory epithelium and olfactory nerve terminals in the bulb. Bromocriptine, a D2 receptor agonist, was added to olfactory epithelium membrane preparations from normal and unilaterally bulbectomized adult rats and the preparations were assayed for forskolin-stimulated adenylyl cyclase activity. In unoperated animals bromocriptine significantly inhibited adenylyl cyclase activity, and the inhibition was abolished following pertussis toxin treatment. In mucosa from unilaterally bulbectomized animals we saw significantly lower adenylyl cyclase activity on the operated side and a further decrease in response to bromocriptine.The data indicate that bromocriptine decreases adenylyl cyclase activity in olfactory tissue, specifically in the sensory neurons, and the reaction is dependent on a pertussis toxin-sensitive G-protein. Given the absence of dopaminergic input to the olfactory epithelium, we propose that dopamine D2 receptors are more probably functionally linked to the adenylyl cyclase that is being transported to the axon terminals than to the adenylyl cyclase in cilia. The results also suggest that receptors are coupled to G-proteins before they are transported to nerve terminals.