Cyclic AMP mediation of the excitatory effect of serotonin in the heart of Aplysia
Cyclic AMP mediation of the excitatory effect of serotonin in the heart of Aplysia
复制标题
环AMP介导海兔心脏中血清素的兴奋作用
DOI：
10.1016/0006-8993(79)90792-3
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发表时间：
1979
期刊：
影响因子：
2.9
通讯作者：
K. Weiss
中科院分区：
文献类型：
--
作者：
D. Mandelbaum;J. Koester;M. Schonberg;K. Weiss
一种神经递质可以在同一神经系统内的不同位置兴奋或抑制，这一证明提出了一个问题，即为什么动物使用几种不同类型的神经递质。原则上，一种单一的递质物质可能能够调节神经系统的所有综合功能。存在多个递质的一个看似合理的原因是，特定递质的突触后受体可能适用于执行一种特殊类型的突触转导4。例如，在后桥海兔，已发现大量使用5-羟色胺(5-HT)的突触。在这些突触中，5-羟色胺的突触后作用有一个非常慢的起始和偏移时间2、10、16、~0、23、31，在某些情况下似乎不是5-羟色胺对静息膜传导16、a0的直接影响。这些不寻常的突触效应中，有许多似乎是由第二信使3‘，5’环磷酸腺苷(CAMP)2，16，2a等间接介导的。在3个这样的突触上，5-羟色胺的作用不是通过直接刺激或抑制突触后细胞，而是通过调节由单独的通路16、21、23、30启动的递质释放或肌肉收缩等过程来发挥作用。这些结果表明，在海兔，5-羟色胺可能优先存在于突触，突触后细胞的紧张性调制是通过细胞内cAMP的增加而实现的。我们通过研究5-羟色胺在5-羟色胺能心脏兴奋细胞RBHE20、21和心脏之间的突触的作用机制来检验这一想法。RBHE的活动通过一种起效缓慢但持续时间较长的机制引起肌源性心跳频率的增加2L我们的实验旨在确定RBHE活动对心率的这种紧张性调制是否由突触后cAMP的变化所介导。在一个初步的实验中，我们试图确定5-羟色胺是否可以促进由标记前体([~3H]腺苷)合成的[~3H]cAMP的积累。这个实验的实验方案已经在前面写过了，最后还包括了对这篇文章的更新
The demonstration that a single neurotransmitter can either excite or inhibit at different loci within the same nervous system raises the question of why animals use several different types of neurotransmitters. In principle, a single transmitter substance might be able to mediate all the integrative functions of the nervous system. One plausible reason for the existence of multiple transmitters is that the postsynaptic receptors to a particular transmitter may be adapted to perform a specialized type of synaptic transduction 4. In the opisthobranch Aplysia, for example, a large number of synapses have been identified that use serotonin (5-HT). At a relatively large percentage of these synapses the postsynaptic action of 5-HT has a very slow onset and offset time2, 10, 16,~ 0, 23, 31 and in some cases appears not to result from a direct effect of 5-HT on resting membrane conductance16, a0. Many of these unusual synaptic effects of 5-HT appear to be mediated indirectly by the second messenger 3', 5'cyclic adenosine monophosphate (cAMp) 2, 16, 2a, al. At 3 such synapses 5-HT has been shown to exert its effects not by directly exciting or inhibiting the postsynaptic cell, but rather by modulating a process such as transmitter release or muscle contraction that is initiated by a separate pathway16, 21, 23, 30. These results indicate that in Aplysia 5-HT may be found preferentially at synapses where tonic modulation of the postsynaptic cell is brought about by an increase in intracellular cAMP. We tested this idea by examining the mechanism of 5-HT action, in, 4plysia californica, at a synapse between the serotonergic heart-excitatory cell RBHE20, 2l and the heart. Activity in RBHE causes an increase in the rate of the myogenic heart beat by a mechanism that is slow in onset, but of long duration2L Our experiments were designed to determine whether this tonic modulation of heart rate by RBHE activity is mediated by postsynaptic changes in cAMP. In a preliminary experiment we attempted to determine whether serotonin could enhance the accumulation of [3H] cAMP synthesized from labeled precursor ([3H] adenosine). The experimental protocol for this experiment has been previously i An update to this article is included at the end