Somatostatin blocks Ca2+ action potential activity in prolactin-secreting pituitary tumor cells through coordinate actions on K+ and Ca2+ conductances.
Somatostatin blocks Ca2+ action potential activity in prolactin-secreting pituitary tumor cells through coordinate actions on K+ and Ca2+ conductances.
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生长抑素通过协调 K 和 Ca2 电导来阻断催乳素分泌垂体肿瘤细胞中的 Ca2 动作电位活性。
作者：
Patrice Mollard;Pierre Vacher;Bernard Dufy;Jeffery L. Barker
下丘脑肽生长抑素（SRIF）抑制表型不同的垂体内分泌细胞的分泌活性。我们使用全细胞记录技术研究了肽对大鼠垂体瘤细胞（GH3/B6）和人类腺瘤的电特性的影响，这些细胞以srif敏感的方式分泌人类PRL。两种细胞类型对SRIF的电生理特性和电反应在质量上相似。在实验条件下，大多数细胞自发产生Ca2+依赖性动作电位。多肽对细胞兴奋性的作用受到马血清和胎牛血清的显著影响。如果没有这些添加剂，电反应就会减弱，无法进行详细的研究。因此，在含有血清的培养基中进行记录。在血清存在的情况下，几乎所有细胞都自发产生Ca2+动作电位，并且肽诱导的兴奋性变化得到了很好的保存。在降低细胞内游离钙（[Ca2+]i）和抑制基础PRL释放的浓度下，SRIF以剂量依赖的方式抑制自发和诱发动作电位活性。电流和电压箝位实验揭示了肽对可激膜特性的协同作用。SRIF （1 nM）增强了去极化激活，迅速灭活向外K+电流，从而有效地降低了动作电位发生的速率。在10-1000 nM范围内，SRIF在很宽的膜电位范围内缓慢激活了几乎不灭活的K+电导。这有效地超极化细胞远离阈值触发Ca2+依赖的动作电位和分流膜。在全细胞记录的细胞内透析过程中，在静息电位水平激活的肽诱导的K+电导逐渐丧失。膜片移液管中包含的细胞的稀水裂解物阻止了srif诱导的电反应的大部分破坏，而包含的atp再生系统保留了一些肽的作用。在10-100 nM浓度范围内，SRIF还降低了电压依赖性Ca2+电流。此外，百日咳毒素预处理细胞可消除SRIF对细胞兴奋性的作用，提示SRIF可通过gtp结合蛋白（G蛋白）调节离子通道的功能。结果表明，SRIF协同作用于肿瘤PRL细胞中表达的初级电导，以减弱或阻止Ca2+动作电位的产生，从而阻止细胞外来源的Ga2+进入。（摘要删节为400字）
The hypothalamic peptide somatostatin (SRIF) suppresses secretory activity in phenotypically distinct pituitary endocrine cells. We have used tight-seal whole-cell recording techniques to study the peptide's effects on the electrical properties of tumor pituitary cells derived from rat (GH3/B6) and human adenomas that secrete human PRL in a SRIF-sensitive manner. Both cell types exhibited qualitatively similar electrophysiological properties and electrical responses to SRIF. Under the experimental conditions employed the majority of cells spontaneously generated Ca2+-dependent actions potentials. The actions of the peptide on cellular excitability were markedly affected by the presence of horse and fetal calf sera. Without these additives the electrical responses faded and could not be studied in detail. Therefore, recordings were conducted in media containing sera. In the presence of sera almost all cells spontaneously generated Ca2+ action potentials, and peptide-induced changes in excitability were well preserved. SRIF depressed spontaneous and evoked action potential activity in a dose-dependent manner at concentrations that reduced intracellular free calcium ([Ca2+]i) and suppressed basal PRL release. Current and voltage clamp experiments revealed coordinate actions of the peptide on excitable membrane properties. SRIF (1 nM) enhanced a depolarization-activated, rapidly inactivating outward K+ current, thereby effectively reducing the rate at which action potentials occurred. Over the 10-1000 nM range SRIF slowly activated a virtually noninactivating K+ conductance over a wide range of membrane potential. This effectively hyperpolarized cells away from the threshold for triggering Ca2+-dependent action potentials and shunted the membrane. The peptide induced K+ conductance activated at the level of the resting potential was progressively lost during the intracellular dialysis of whole-cell recording. Dilute aqueous lysates of cells included in the patch pipette prevented much of the rundown of this SRIF-induced electrical response while inclusion of an ATP-regenerating system preserved some of the peptide action. Over the 10-100 nM concentration range SRIF also reduced voltage-dependent Ca2+ current. Furthermore, pretreatment of cells with pertussis toxin abolished SRIF action on cellular excitability, suggesting that SRIF can regulate the function of ionic channels through GTP-binding proteins (G proteins). The results demonstrate that SRIF acts coordinately on the primary conductances expressed in tumor PRL cells to attenuate or block Ca2+ action potential generation and thus Ga2+ entry from extracellular sources.(ABSTRACT TRUNCATED AT 400 WORDS)
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克隆垂体细胞中促甲状腺素释放激素对 K 通道的双重调节。
DOI：
10.1073/pnas.82.12.4282
发表时间：
1985
影响因子：
11.1
作者：
Dubinsky,JM;Oxford,GS
通讯作者：
Oxford,GS
百日咳毒素可阻断生长抑素的环 AMP 介导和环 AMP 独立作用。
DOI：
--
发表时间：
1985
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Koch,BD;Dorflinger,LJ;Schonbrunn,A
通讯作者：
Schonbrunn,A
克隆大鼠垂体前叶细胞膜中分离的 GK 蛋白重建生长抑素和毒蕈碱受体介导的 K 通道刺激。
DOI：
10.1210/mend-1-4-283
发表时间：
1987
期刊：
Molecular endocrinology (Baltimore, Md.)
影响因子：
--
作者：
Yatani,A;Codina,J;Sekura,RD;Birnbaumer,L;Brown,AM
通讯作者：
Brown,AM
生长抑素通过不同机制抑制 GH 垂体细胞中基础和血管活性肠肽刺激的激素释放。
影响因子：
4.8
作者：
Dorflinger,LJ;Schonbrunn,A
通讯作者：
Schonbrunn,A
影响因子：
18.2
作者：
Patel,YC;Srikant,CB
通讯作者：
Srikant,CB