Konishi S, Song S Y, Ogawa T, Kanazawa I
Department of Neuroscience, Mitsubishi Kasei Institute of Life Sciences, Tokyo, Japan.
Neurosci Res. 1992 Jul;14(2):81-95. doi: 10.1016/0168-0102(92)90085-q.
Using intracellular recording, we examined the effects of three mammalian tachykinins, substance P (SP), neurokinin A (NKA), and neurokinin B (NKB), on sympathetic neurons of isolated rat coeliac-superior mesenteric ganglia (C-SMG). The 3 tachykinins elicited two distinct depolarizing responses in ganglion cells: fast depolarization with time-to-peak of 1-2 sec and duration of 5-10 sec, and slow depolarization with time-to-peak of about 20 sec and duration of 120-140 sec. Both fast and slow responses persisted in a solution containing low Ca2+ and high Mg2+ or tetrodotoxin, which indicates that the tachykinins directly act on ganglion cells to produce fast and slow depolarizations. The two types of tachykinin-induced responses exhibited clearly distinguishable properties. The membrane conductance was increased during the fast response, but not significantly changed, slightly decreased or sometimes increased during the slow response. Within certain range of membrane potential, the amplitude of fast response increased upon membrane hyperpolarization and decreased upon depolarization of ganglion cells. In contrast, the amplitude of slow response associated with membrane conductance decrease was increased with membrane depolarization and decreased with hyperpolarization. The fast response was markedly suppressed in a Na(+)-deficient solution, a solution containing nominally zero Ca2+ (plus 0.1 mM EGTA in some cases), and in a solution containing Cd2+ or Mn2+, whereas the slow response was not affected in these solutions and was augmented in some cells in K(+)-free solution. Thus it seems that the increase in Ca(2+)-dependent cationic conductance underlies the fast response and that the slow response is produced at least in part by suppression of certain K+ channels. The fast response progressively decreased in amplitude upon repeated application of the peptides with short intervals, whereas the slow response was rather augmented by repeated application. Lowering the temperature markedly depressed the slow response, while the fast response remained almost unaffected. It is therefore likely that the fast and slow depolarizations are mediated by two different subtypes of tachykinin receptors or a single class of receptors linked with two different intracellular mechanisms. Measurement of tachykinins in several sympathetic ganglia by combined use of HPLC and radioimmunoassay revealed that the highest amount of SP occurs in the C-SMG where the content of SP (136.0 pmol/g protein) was higher than those of NKA (44.3) and NKB (18.7). SP thus appears to function as a major tachykinin in rat C-SMG.
我们采用细胞内记录法，研究了三种哺乳动物速激肽，即P物质（SP）、神经激肽A（NKA）和神经激肽B（NKB）对离体大鼠腹腔-肠系膜上神经节（C-SMG）交感神经元的影响。这三种速激肽在神经节细胞中引发了两种不同的去极化反应：快速去极化，其峰值时间为1 - 2秒，持续时间为5 - 10秒；以及缓慢去极化，其峰值时间约为20秒，持续时间为120 - 140秒。在含有低Ca2+和高Mg2+或河豚毒素的溶液中，快速和缓慢反应均持续存在，这表明速激肽直接作用于神经节细胞以产生快速和缓慢去极化。这两种由速激肽诱导的反应表现出明显可区分的特性。快速反应期间膜电导增加，但在缓慢反应期间膜电导无显著变化、略有下降或有时增加。在一定的膜电位范围内，神经节细胞膜超极化时快速反应的幅度增加，而去极化时则减小。相反，与膜电导降低相关的缓慢反应幅度随膜去极化而增加，随超极化而减小。快速反应在缺乏Na+的溶液、含有名义上零Ca2+（某些情况下加0.1 mM EGTA）的溶液以及含有Cd2+或Mn2+的溶液中被显著抑制，而缓慢反应在这些溶液中不受影响，并且在无K+溶液中某些细胞中增强。因此，似乎Ca(2+)依赖性阳离子电导的增加是快速反应的基础，而缓慢反应至少部分是由某些K+通道的抑制所产生。当短时间间隔重复应用这些肽时，快速反应的幅度逐渐减小，而缓慢反应则因重复应用而增强。降低温度显著抑制缓慢反应，而快速反应几乎不受影响。因此，快速和缓慢去极化可能由两种不同亚型的速激肽受体介导，或者由与两种不同细胞内机制相连的单一类受体介导。通过高效液相色谱（HPLC）和放射免疫测定法联合测量几种交感神经节中的速激肽，结果显示C-SMG中SP的含量最高，其中SP的含量（136.0 pmol/g蛋白质）高于NKA（44.3）和NKB（18.7）。因此，SP似乎在大鼠C-SMG中作为主要的速激肽发挥作用。
