Roussel J P, Mateu G, Astier H
Laboratoire de Neurobiologie Endocrinologique, URA 1197 CNRS, Université de Montpellier 2, France.
Endocr Regul. 1992 Dec;26(4):163-70.
The aim of the present study was to determine the functional relationship between blockade of potassium or calcium channel activity and the initial burst of TSH secretion in response to TRH. Perifused rat pituitary fragments were stimulated by a 6-min pulse of physiological concentration of TRH (10 nM) in the presence or absence of pharmacological blockers of K+ or Ca2+ channels. Blockade of Ca(2+)-activated K+ channels with TEA (10 mM and 30 mM), apamin (200 nM), or charybdotoxin (50 nM) completely or partially blunted TRH-induced TSH release. By contrast, blockade of voltage-dependent K+ channels with 4-aminopyridine (4-AP) (500 microM) or with dendrotoxin (DTX) (350 nM) significantly increased TSH response. Moreover, blockade of T-type voltage-sensitive Ca2+ channels (VSCC) with NiCl (3 mM) or with diphenylhydantoin (100 microM) significantly (P < 0.01) reduced TSH response to TRH, whereas blockade of L-type Ca2+ channels with verapamil (50 microM) was ineffective. Our results suggest that secretion of TSH in response to nanomolar concentrations of TRH is correlated with stimulation of Ca(2+)-activated K+ channels, and inhibition of 4-AP-and DTX-sensitive voltage-dependent K+ channels; furthermore TSH response seems to depend on the activation of T-type VSCC.
本研究的目的是确定钾通道或钙通道活性阻断与促甲状腺激素释放激素(TRH)刺激下促甲状腺激素(TSH)分泌初始爆发之间的功能关系。在存在或不存在K⁺或Ca²⁺通道药理学阻断剂的情况下,用生理浓度的TRH(10 nM)进行6分钟脉冲刺激灌流的大鼠垂体片段。用四乙铵(TEA,10 mM和30 mM)、蜂毒明肽(200 nM)或大蝎毒素(50 nM)阻断Ca²⁺激活的K⁺通道可完全或部分减弱TRH诱导的TSH释放。相比之下,用4-氨基吡啶(4-AP,500 μM)或树眼镜蛇毒素(DTX,350 nM)阻断电压依赖性K⁺通道可显著增加TSH反应。此外,用氯化镍(3 mM)或苯妥英(100 μM)阻断T型电压敏感钙通道(VSCC)可显著(P < 0.01)降低TSH对TRH的反应,而用维拉帕米(50 μM)阻断L型钙通道则无效。我们的结果表明,对纳摩尔浓度TRH的反应中TSH的分泌与Ca²⁺激活的K⁺通道的刺激以及4-AP和DTX敏感的电压依赖性K⁺通道的抑制相关;此外,TSH反应似乎依赖于T型VSCC的激活。