Rusko J, Bauer V
Centre of Physiological Sciences, Slovak Academy of Sciences, Bratislava.
Gen Physiol Biophys. 1988 Jun;7(3):263-79.
The interaction between phenylephrine and calcium entry blockers was studied on the taenia of the guinea-pig caecum using the double sucrose gap method. Sustained hyperpolarization, relaxation and attenuation of evoked electrical and mechanical activity were induced by non-cumulative addition of phenylephrine (0.1 to 250 mumol.1-1) for 2 to 4 min. When the alpha 1-adrenoceptor agonist was applied for a prolonged period (20 to 60 min) the initial inhibitory response gradually disappeared both at room temperature and at 32 degrees C. The renewed action potentials were accompanied by a positive afterpotential. The initial hyperpolarization and its delayed recovery in course of the phenylephrine effect were significantly reduced in calcium-free medium containing EDTA (2 mmol.1-1), after pretreatment with nifedipine (0.1 to 1 mumol.1-1), verapamil (10 to 100 mumol.1-1) or procaine (0.5 to 2 mmol.1-1). In contrast sodium nitroprusside (10 to 100 mumol.1-1) which produced biphasic changes similar to those of phenylephrine, did not affect the initial and delayed phase of phenylephrine action. Ba2+(5 mmol.1-1) could substitute for Ca2+ in the generation of action potentials but could not substitute for Ca2+ in the mechanisms responsible for the initial and delayed recovery phase of phenylephrine effects. In the presence of La3+ and Mn2+ (0.5 to 3 mmol.1-1) the phenylephrine effects were reduced. In contrast, in the presence of extracellular Ca2+, pretreatment with Mg2+ (12 mmol.1-1) or Ba2+ (5 mmol.1-1) did not affect the action of phenylephrine. It is concluded that activation of alpha 1-adrenoceptors results in the release of Ca2+ from an intracellular store, which leads to the opening od TEA-sensitive potassium channels, causing the initial phase of alpha 1-adrenoceptor action. Ca2+ is loaded into this intracellular store by entering the cell through the potential sensitive calcium channels. Although the mechanisms responsible for the delayed phase could not be clarified, its dependence on the presence of the initial phase is apparent.
采用双蔗糖间隙法，在豚鼠盲肠带研究了去氧肾上腺素与钙通道阻滞剂之间的相互作用。通过非累积添加去氧肾上腺素（0.1至250μmol·L⁻¹）2至4分钟，可诱导出持续的超极化、舒张以及诱发的电活动和机械活动的衰减。当α₁ - 肾上腺素能受体激动剂长时间应用（20至60分钟）时，在室温及32℃下，初始抑制反应均逐渐消失。再次出现的动作电位伴有正后电位。在用硝苯地平（0.1至1μmol·L⁻¹）、维拉帕米（10至100μmol·L⁻¹）或普鲁卡因（0.5至2mmol·L⁻¹）预处理后，在含EDTA（2mmol·L⁻¹）的无钙培养基中，去氧肾上腺素作用过程中的初始超极化及其延迟恢复均显著降低。相比之下，硝普钠（10至100μmol·L⁻¹）产生与去氧肾上腺素类似的双相变化，但不影响去氧肾上腺素作用的初始阶段和延迟阶段。Ba²⁺（5mmol·L⁻¹）可在动作电位产生过程中替代Ca²⁺，但在去氧肾上腺素作用的初始和延迟恢复阶段的机制中不能替代Ca²⁺。在La³⁺和Mn²⁺（0.5至3mmol·L⁻¹）存在时，去氧肾上腺素的作用减弱。相反，在细胞外Ca²⁺存在时，用Mg²⁺（12mmol·L⁻¹）或Ba²⁺（5mmol·L⁻¹）预处理不影响去氧肾上腺素的作用。结论是，α₁ - 肾上腺素能受体的激活导致Ca²⁺从细胞内储存库释放，这导致对TEA敏感的钾通道开放，引起α₁ - 肾上腺素能受体作用的初始阶段。Ca²⁺通过电位敏感钙通道进入细胞而被加载到这个细胞内储存库中。虽然延迟阶段的机制尚不清楚，但其对初始阶段存在的依赖性是明显的。
