Maggi C A, Giuliani S, Santicioli P, Tramontana M, Meli A
Pharmacology Department, A. Menarini Pharmaceuticals, Florence, Italy.
Neuroscience. 1990;34(1):243-50. doi: 10.1016/0306-4522(90)90318-x.
The aim of this study was to assess whether omega conotoxin fraction GVIA, a potent blocker of N- and L-type voltage-sensitive calcium channels, might interfere with reflex responses (micturition, blood pressure rise in spinal rats) produced by activation of capsaicin-sensitive sensory nerves of the rat urinary bladder. The effect of conotoxin was also investigated on reflex micturition persisting after capsaicin pretreatment. Following topical application onto the bladder, conotoxin did not affect the volume threshold to elicit micturition although it reduced the amplitude of volume-evoked bladder contractions. Likewise, topical conotoxin did not prevent the reflex rise in blood pressure elicited by sudden bladder distension or topical application of capsaicin onto the bladder. In contrast, topical lidocaine strongly prevented both reflex responses. After intrathecal administration, conotoxin produced a dose-dependent inhibition of volume-evoked bladder contractions and the cardiovascular reflex produced by mechanical or chemical stimulation of bladder nerves. Intrathecal conotoxin inhibited micturition also in rats pretreated with capsaicin (50 mg/kg s.c., 4 days before). Depolarization by high potassium (80 mM) produced release of both substance P- and calcitonin gene-related peptide-like immunoreactivity from superfused slices of the dorsal half of rat spinal cord. Capsaicin (1 microM) produced a similar effect, and a previous exposure to capsaicin prevented the effect of potassium. Conotoxin (0.1 microM) significantly reduced (about 50%) the potassium-induced release of neuropeptides from the dorsal half of the rat spinal cord. These findings indicate that conotoxin-sensitive calcium channels in the rat spinal cord play a role in the neurotransmission along reflex pathways activated by stimulation of capsaicin-sensitive nerves in the urinary bladder.(ABSTRACT TRUNCATED AT 250 WORDS)
本研究的目的是评估ω-芋螺毒素GVIA（一种强效的N型和L型电压敏感性钙通道阻滞剂）是否会干扰激活大鼠膀胱辣椒素敏感感觉神经所产生的反射反应（脊髓大鼠的排尿、血压升高）。还研究了芋螺毒素对辣椒素预处理后持续存在的反射性排尿的影响。将芋螺毒素局部应用于膀胱后，虽然它降低了容量诱发的膀胱收缩幅度，但并未影响引发排尿的容量阈值。同样，局部应用芋螺毒素并不能阻止突然膀胱扩张或膀胱局部应用辣椒素所引发的反射性血压升高。相比之下，局部应用利多卡因可强烈阻止这两种反射反应。鞘内给药后，芋螺毒素对容量诱发的膀胱收缩以及机械或化学刺激膀胱神经所产生的心血管反射产生剂量依赖性抑制。鞘内注射芋螺毒素对预先用辣椒素（50mg/kg皮下注射，4天前）处理的大鼠的排尿也有抑制作用。高钾（80mM）去极化可使大鼠脊髓背侧半部分的灌流切片释放P物质和降钙素基因相关肽样免疫反应性物质。辣椒素（lμM）产生类似的作用，且预先接触辣椒素可阻止钾的作用。芋螺毒素（0.1μM）可显著降低（约50%）钾诱导的大鼠脊髓背侧半部分神经肽释放。这些发现表明大鼠脊髓中对芋螺毒素敏感的钙通道在由膀胱中辣椒素敏感神经刺激所激活的反射通路的神经传递中起作用。（摘要截短于250字）
