Knoper S R, Meehan A G, Purnyn S, Coggan J S, Anthony T L, Kreulen D L
Department of Pharmacology, College of Medicine, University of Arizona, Tucson 85724.
Eur J Pharmacol. 1993 Feb 23;232(1):65-9. doi: 10.1016/0014-2999(93)90729-2.
The effect of cholecystokinin octapeptide (CCK-8) was examined in guinea-pig celiac ganglion (CG) neurons in primary culture using standard intracellular recording techniques. Sulfated CCK-8 (CCK-8S; 1 microM) evoked slow depolarizing responses in 94% of CG neurons tested. In contrast, membrane potential was not affected by nonsulfated CCK-8 (CCK-8NS; 1 microM), CCK tetrapeptide (CCK-4; 1 microM), or gastrin (1 microM). The selective CCKA receptor antagonist L 364,718 potently inhibited CCK-8S-induced slow depolarizations (IC50 2.9 pM). In contrast, the selective CCKB receptor antagonist L 365,260 was a weak inhibitor of CCK-8S-induced slow depolarizations (IC50 1.3 microM). The depolarizing responses to CCK-8S were associated with an average increase in cell input resistance of 61%. Single electrode voltage clamp experiments indicated that CCK-8S-induced depolarizations were associated with a slow inward shift in holding current. Thus, the present findings indicate that guinea-pig cultured CG neurons are endowed with excitatory CCKA receptors the activation of which elicits a decrease in membrane conductance, thereby resulting in slow depolarizations.
运用标准的细胞内记录技术，在原代培养的豚鼠腹腔神经节（CG）神经元中检测了八肽胆囊收缩素（CCK - 8）的作用。硫酸化CCK - 8（CCK - 8S；1微摩尔）在94%的受试CG神经元中诱发了缓慢的去极化反应。相比之下，非硫酸化CCK - 8（CCK - 8NS；1微摩尔）、四肽胆囊收缩素（CCK - 4；1微摩尔）或胃泌素（1微摩尔）对膜电位没有影响。选择性CCKA受体拮抗剂L 364,718能有效抑制CCK - 8S诱导的缓慢去极化（半数抑制浓度为2.9皮摩尔）。相比之下，选择性CCKB受体拮抗剂L 365,260对CCK - 8S诱导的缓慢去极化的抑制作用较弱（半数抑制浓度为1.3微摩尔）。对CCK - 8S的去极化反应伴随着细胞输入电阻平均增加61%。单电极电压钳实验表明，CCK - 8S诱导的去极化与钳制电流的缓慢内向偏移有关。因此，目前的研究结果表明，豚鼠培养的CG神经元具有兴奋性CCKA受体，其激活会导致膜电导降低，从而引起缓慢的去极化。
