Yang X P, Chiba S
Department of Pharmacology, Shinshu University School of Medicine, Matsumoto 390-8621, Japan.
Br J Pharmacol. 2000 Jan;129(1):47-52. doi: 10.1038/sj.bjp.0702989.
The actions of omega-conotoxin (omega-CTX) and diltiazem on adrenergic and purinergic components of double peaked vasoconstrictor responses to periarterial nerve stimulation have been investigated in the isolated, perfused canine splenic arterial preparation. Double peaked vasoconstrictions (biphases of vasoconstrictors) were consistently observed in the conditions of 30 s trains of pulses at 1 - 10 Hz frequencies. omega-CTX (1 - 30 nM) produced similar inhibitory effects on the first phase and second phase responses in a dose-related manner. Thirty nM omega-CTX almost completely inhibited the biphasic vasoconstrictions at any used frequencies but did not affect the vasoconstrictor responses to exogenous applied ATP (0.01 - 1 micromol) and noradrenaline (0.03 - 3 nmol). Intraluminal application of a large dose of diltiazem (3 - 10 microM) also produced a dose-dependent inhibitory effect on biphasic vasoconstrictions at any used frequencies. Three microM diltiazem exerted rather a larger inhibitory effect on the second phase than the first phase response at low frequencies (1 - 3 Hz), but a similar inhibition on first and second phasic responses at high frequencies (6 - 10 Hz). An extremely high dose of diltiazem (10 microM) almost completely inhibited the biphasic vasoconstrictor responses to nerve stimulation, and slightly inhibited the contractile responses to exogenous applied ATP (0.01 - 1 micromol) and noradrenaline (0.03 - 3 nmol). The present results indicate that omega-CTX selectively acts prejunctionally to inhibit the release of transmitters from sympathetic nerve terminals, and omega-CTX-sensitive calcium channels may produce a parallel controlling of purinergic and adrenergic components of sympathetic cotransmission. A large dose of diltiazem has inhibitory effects on both prejunctional and postjunctional sympathetic co-transmission. British Journal of Pharmacology (2000) 129, 47 - 52
在离体灌注犬脾动脉标本中，研究了ω-芋螺毒素（ω-CTX）和地尔硫䓬对动脉周围神经刺激引起的双相血管收缩反应中肾上腺素能和嘌呤能成分的作用。在1 - 10Hz频率下施加30s的脉冲串条件下， consistently观察到双相血管收缩（血管收缩剂的双相性）。ω-CTX（1 - 30 nM）以剂量相关的方式对第一相和第二相反应产生类似的抑制作用。30 nM ω-CTX几乎完全抑制了任何使用频率下的双相血管收缩，但不影响对外源性施加的ATP（0.01 - 1 μmol）和去甲肾上腺素（0.03 - 3 nmol）的血管收缩反应。腔内应用大剂量地尔硫䓬（3 - 10 μM）也对任何使用频率下的双相血管收缩产生剂量依赖性抑制作用。3 μM地尔硫䓬在低频（1 - 3Hz）时对第二相的抑制作用比对第一相反应的抑制作用更大，但在高频（6 - 10Hz）时对第一相和第二相反应的抑制作用相似。极高剂量的地尔硫䓬（10 μM）几乎完全抑制了对神经刺激的双相血管收缩反应，并轻微抑制了对外源性施加的ATP（0.01 - 1 μmol）和去甲肾上腺素（0.03 - 3 nmol）的收缩反应。目前的结果表明，ω-CTX选择性地在节前起作用，抑制交感神经末梢递质的释放，并且ω-CTX敏感的钙通道可能对交感神经共同传递的嘌呤能和肾上腺素能成分产生平行控制。大剂量地尔硫䓬对节前和节后交感神经共同传递均有抑制作用。《英国药理学杂志》（2000年）129卷，47 - 52页
