Omega conotoxin and prejunctional modulation of the biphasic response of the rat isolated urinary bladder to single pulse electrical field stimulation.
作者信息
Maggi C A
机构信息
Pharmacology Department, A. Menarini Pharmaceuticals, Florence, Italy.
出版信息
J Auton Pharmacol. 1991 Oct;11(5):295-304. doi: 10.1111/j.1474-8673.1991.tb00253.x.
Single pulse electrical field stimulation (EFS) produces a biphasic response of muscle strips of the rat isolated urinary bladder consisting of an early and a late contraction which were atropine-resistant and atropine-sensitive, respectively. Repeated application of desensitizing doses of the P2 purinoceptor agonist, alpha, beta-methylene ATP (mATP) inhibited the early response while leaving unaffected the late component. 2. Omega conotoxin (CTX, 0.1 microM) inhibited both the early and the late response either in control conditions or after enhancement by physostigmine (0.1 microM). The effect of CTX was, in both cases, more pronounced on the late than the early response to EFS. CTX (0.1 microM) failed to affect contraction produced by ATP or acetylcholine at concentrations (0.3 mM and 0.5 microM) which produced a response similar to that to EFS. 3. The effect of physostigmine was more intense for the late than the early response and was abolished by atropine. In the presence of CTX, physostigmine enhanced both the early and the late components of the mechanical response to EFS. 4. Nifedipine (0.1-1 microM) reduced to a similar extent both the early and late responses. Bay K 8644 (1 microM) produced a marked enhancement of the response to EFS, which, however, did not have a distinct late peak. In the presence of Bay K 8644, either atropine (3 microM) or tetrodotoxin (1 microM) had minor inhibitory effects indicating the myogenic origin of the response. 5. Neurokinin A (0.1-1 nM) enhanced both the early and late responses to EFS without affecting the contraction produced by exogenous acetylcholine or ATP. A consistent potentiation was evident also in the presence of CTX and for the early response, in the presence of atropine. Clonidine (3 microM) inhibited the response to EFS either in the absence or the presence of physostigmine. The inhibitory effect of clonidine, shown previously to depend upon activation of prejunctional alpha 2-adrenoceptors, was still observed in presence of CTX or atropine. 6. It is concluded that CTX-sensitive voltage dependent calcium channels play a more important role in determining the cholinergic rather than the non-cholinergic, putatively purinergic, component of the biphasic response of the rat bladder to single pulse EFS. The action of CTX is likely to be exerted on N-type rather than L-type (dihydropyridine-sensitive) calcium channels. Prejunctional modulation (enhancement by neurokinin A, inhibition by clonidine) occurs even in the presence of CTX-sensitive channels blockade.
摘要
单脉冲电场刺激（EFS）可使大鼠离体膀胱的肌肉条产生双相反应，包括早期收缩和晚期收缩，前者对阿托品不敏感，后者对阿托品敏感。重复给予脱敏剂量的P2嘌呤受体激动剂α,β-亚甲基ATP（mATP）可抑制早期反应，而不影响晚期成分。2. ω-芋螺毒素（CTX，0.1微摩尔）在对照条件下或经毒扁豆碱（0.1微摩尔）增强后，均可抑制早期和晚期反应。在这两种情况下，CTX对EFS晚期反应的影响比对早期反应更明显。CTX（0.1微摩尔）在浓度为0.3毫摩尔和0.5微摩尔时，未能影响ATP或乙酰胆碱所产生的收缩，而这两种浓度的ATP或乙酰胆碱所产生的反应与EFS所产生的反应相似。3. 毒扁豆碱对晚期反应的作用比对早期反应更强，且可被阿托品消除。在存在CTX的情况下，毒扁豆碱增强了对EFS机械反应的早期和晚期成分。4. 硝苯地平（0.1 - 1微摩尔）对早期和晚期反应的降低程度相似。Bay K 8644（1微摩尔）使对EFS的反应显著增强，然而，该反应没有明显的晚期峰值。在存在Bay K 8644的情况下，阿托品（3微摩尔）或河豚毒素（1微摩尔）的抑制作用较小，表明该反应起源于肌源性。5. 神经激肽A（0.1 - 1纳摩尔）增强了对EFS的早期和晚期反应，而不影响外源性乙酰胆碱或ATP所产生的收缩。在存在CTX的情况下以及对于早期反应，在存在阿托品的情况下，也明显存在持续的增强作用。可乐定（3微摩尔）在不存在或存在毒扁豆碱的情况下，均抑制对EFS的反应。可乐定的抑制作用先前已表明取决于节前α2-肾上腺素能受体的激活，在存在CTX或阿托品的情况下仍可观察到。6. 得出结论，CTX敏感的电压依赖性钙通道在决定大鼠膀胱对单脉冲EFS双相反应的胆碱能成分而非非胆碱能（推测为嘌呤能）成分方面发挥更重要的作用。CTX的作用可能是作用于N型而非L型（对二氢吡啶敏感）钙通道。即使在存在CTX敏感通道阻断的情况下，也会发生节前调节（神经激肽A增强作用，可乐定抑制作用）。
