Modulation of guinea pig intrinsic cardiac neurons by prostaglandins
Modulation of guinea pig intrinsic cardiac neurons by prostaglandins
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DOI：
10.1152/ajpregu.00123.2003
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发表时间：
2003-09-01
影响因子：
2.8
通讯作者：
Hardwick, JC
中科院分区：
文献类型：
--
作者：
Jelson, GS;DeMasi, GM;Hardwick, JC
心脏肥大细胞的激活已显示通过组胺受体的激活改变交感神经元功能。本研究检测了野牡丹素改变豚鼠心内神经元活性的能力。从整个心脏丛的细胞内电压记录表明，抗原介导的肥大细胞脱粒产生后超极化（AHP）的衰减，这是由磷脂酶A（2）抑制剂5，8，11，14-二十碳四炔酸阻止。外源性PGD（2）或PGE（2）均引起膜电位的双相变化，并抑制AHP的幅度和持续时间。使用浴灌流（1 μ M PGE（2）和PGD（2））、特异性激动剂（BW 245 C、硫前列酮和布他前列素）和拮抗剂（AH 6809和SC 19220）检查前列腺素受体，发现PGE（2）特异性EP 2和EP 3受体的证据，但没有EP 1或PGD（2）特异性前列腺素（DP）受体的证据。磺前列酮能够在某些细胞中模拟PGE（2）反应，但不是在所有PGE（2）敏感细胞中。布他前列素能够模拟PG诱导的某些细胞超极化，但不改变AHP。用TEA、Charybdotoxin或apamin抑制特异性钾通道表明，TEA和Charybdotoxin均不能阻止PGE（2）诱导的AHP衰减。Apamin单独抑制AHP持续时间，PG在这些细胞中没有进一步的影响。这些结果表明，豚鼠心内神经元可以调制PG，最有可能通过EP 2，EP 3，或潜在的EP 4受体，这种反应是由于，至少部分地，在小电导K-Ca电流的减少。
Activation of cardiac mast cells has been shown to alter para-sympathetic neuronal function via the activation of histamine receptors. The present study examined the ability of prostaglandins to alter the activity of guinea pig intracardiac neurons. Intracellular voltage recordings from whole mounts of the cardiac plexus showed that antigen-mediated mast cell degranulation produces an attenuation of the afterhyperpolarization (AHP), which was prevented by the phospholipase A(2) inhibitor 5,8,11,14-eicosatetraynoic acid. Exogenous application of either PGD(2) or PGE(2) produced a biphasic change in the membrane potential and an inhibition of both AHP amplitude and duration. Examination of prostanoid receptors using bath perfusions (1 muM PGE(2) and PGD(2)), specific agonists (BW245C, sulprostone, and butaprost), and antagonists (AH6809 and SC19220) found evidence for both the PGE(2)-specific EP2 and EP3 receptors, but not for EP1 or the PGD(2)-specific prostanoid (DP) receptors. Sulprostone was able to mimic the PGE(2) responses in some cells, but not in all PGE(2)-sensitive cells. Butaprost was able to mimic the PG-induced hyperpolarization in some cells, but did not alter the AHP. Inhibition of specific potassium channels with either TEA, charybdotoxin, or apamin showed that neither TEA nor charybdotoxin could prevent the PGE(2)-induced AHP attenuation. Apamin alone inhibited AHP duration, with PGs having no further effect in these cells. These results demonstrate that guinea pig intracardiac neurons can be modulated by PG, most likely through either EP2, EP3, or potentially EP4 receptors, and this response is due, at least in part, to a reduction in small-conductance K-Ca currents.