缓激肽对大鼠膀胱体内运动的局部和反射反应的药理学分析。

Pharmacological analysis of the local and reflex responses to bradykinin on rat urinary bladder motility in vivo.

作者信息

Lecci A, Giuliani S, Meini S, Maggi C A

机构信息

Pharmacology Research Dept., A. Menarini Pharmaceuticals, Florence, Italy.

出版信息

Br J Pharmacol. 1995 Feb;114(3):708-14. doi: 10.1111/j.1476-5381.1995.tb17196.x.

DOI:10.1111/j.1476-5381.1995.tb17196.x

PMID:7537595

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1510018/

Abstract

The topical application of bradykinin (BK) (0.05-5000 pmol/rat) onto the serosal surface of the urinary bladder in urethane-anaesthetized rats, evoked low amplitude tonic contractions (not exceeding 25 mmHg) or high amplitude (about 50 mmHg), phasic reflex contractions (chemoceptive micturition reflex) which were abolished by bilateral ablation of the pelvic ganglia. In ganglionectomized rats, BK induced only a local, tonic-type contraction. 2. Systemic capsaicin pretreatment (164 mumol kg-1, 4 days before) reduced the incidence of chemoceptive reflex induced by BK (500 pmol/rat) but had no effect on the magnitude of the tonic-type contraction elicited by BK in ganglionectomized rats. Indomethacin (11 mumol kg-1, 20 min before) reduced the incidence but not the amplitude of the reflex contractions induced by topical application of BK (500 pmol/rat). In ganglionectomized rats, indomethacin (11 mumol kg-1, 20 min before) decreased the amplitude of the tonic contraction evoked by BK. Indomethacin did not affect the chemoceptive reflex induced by topical application of capsaicin (15 nmol/rat) onto the bladder. 3. Intrathecal administration of the tachykinin NK1 receptor antagonists, RP 67,580 (10 nmol/rat) or SR 140,333 (10 nmol/rat), abolished the chemoceptive reflex induced by BK without modifying the magnitude of the tonic contraction. SR 140,333 (10 nmol/rat) also abolished the occurrence of the chemoceptive reflex induced by capsaicin. 4. Intravenous administration of the B2 receptor antagonist, Hoe 140 (35 nmol kg-1, 10 min before) abolished the reflex and local effects induced by BK on bladder motility but failed to modify the chemoceptive reflex induced by topical application of capsaicin (15 nmol/rat). 5. Intrathecal administration of Hoe 140 (10 nmol/rat) reduced the incidence of the chemoceptive reflex induced by BK but had no effect on the amplitude of the local motor response. Likewise, Hoe 140(10 nmol/rat, i.t.) reduced the incidence of reflex bladder contractions induced by topical application of capsaicin (15 nmol/rat) without affecting the magnitude of the tonic-type contraction.6. These findings indicate that BK stimulates motility through B2 receptors in the rat urinary bladder.BK activates the reflex response by stimulating capsaicin-sensitive afferent nerves with a contribution from prostanoids. At the spinal cord level, tachykinin NK1 and BK B2 receptors could also be involved in the chemoceptive reflex induced by BK or capsaicin.

摘要

在氨基甲酸乙酯麻醉的大鼠中，将缓激肽（BK）（0.05 - 5000 pmol/大鼠）局部应用于膀胱浆膜表面，可诱发低幅度紧张性收缩（不超过25 mmHg）或高幅度（约50 mmHg）的相性反射收缩（化学感受性排尿反射），双侧切除盆神经节后这些反射收缩消失。在去神经节大鼠中，BK仅诱发局部紧张性收缩。2. 全身性辣椒素预处理（164 μmol·kg⁻¹，4天前）降低了BK（500 pmol/大鼠）诱发的化学感受性反射的发生率，但对去神经节大鼠中BK诱发的紧张性收缩幅度无影响。吲哚美辛（11 μmol·kg⁻¹，20分钟前）降低了局部应用BK（500 pmol/大鼠）诱发的反射收缩的发生率，但不影响其幅度。在去神经节大鼠中，吲哚美辛（11 μmol·kg⁻¹，20分钟前）降低了BK诱发的紧张性收缩的幅度。吲哚美辛不影响局部应用辣椒素（15 nmol/大鼠）于膀胱诱发的化学感受性反射。3. 鞘内注射速激肽NK1受体拮抗剂RP 67,580（10 nmol/大鼠）或SR 140,333（10 nmol/大鼠）可消除BK诱发的化学感受性反射，而不改变紧张性收缩的幅度。SR 140,333（10 nmol/大鼠）也消除了辣椒素诱发的化学感受性反射的发生。4. 静脉注射B2受体拮抗剂Hoe 140（35 nmol·kg⁻¹，10分钟前）可消除BK对膀胱运动性的反射和局部效应，但未能改变局部应用辣椒素（15 nmol/大鼠）诱发的化学感受性反射。5. 鞘内注射Hoe 140（10 nmol/大鼠）降低了BK诱发的化学感受性反射的发生率，但对局部运动反应的幅度无影响。同样，鞘内注射Hoe 140（10 nmol/大鼠）降低了局部应用辣椒素（15 nmol/大鼠）诱发的膀胱反射性收缩的发生率，而不影响紧张性收缩的幅度。6. 这些发现表明，BK通过大鼠膀胱中的B2受体刺激运动性。BK通过刺激辣椒素敏感的传入神经并伴有前列腺素的参与来激活反射反应。在脊髓水平，速激肽NK1和BK B2受体也可能参与BK或辣椒素诱发的化学感受性反射。