Maggi C A, Santicioli P, Del Bianco E, Giuliani S
Pharmacology Department, A. Menarini Pharmaceuticals, Florence, Italy.
J Urol. 1992 Dec;148(6):1944-50. doi: 10.1016/s0022-5347(17)37090-8.
The local motor response to bradykinin and the bacterial chemotactic peptide, formyl-methionyl-leucyl-phenylalanine (FMLP) was investigated in the guinea-pig isolated renal pelvis and ureter in relation to possible activation of capsaicin-sensitive primary afferent nerves and release of sensory neuropeptides. Both bradykinin (1 nM-10 microM) and FMLP (10 nM-10 microM) produced a concentration-dependent positive inotropic effect in the isolated renal pelvis which was unaffected by in vitro capsaicin desensitization. The response to bradykinin was antagonized by HOE 140, a bradykinin receptor antagonist, while it was unaffected by MEN 10,376, a tachykinin receptor antagonist, hCGRP(8-37) a calcitonin gene-related peptide (CGRP) receptor antagonist and N-t-BOC-Phe-DLeu-Phe-DLeu-Phe (BPLPLP), an FMLP antagonist. The response to FMLP was blocked by BPLPLP while it was unaffected by HOE 140, MEN 10,376 or hCGRP(8-37). Indomethacin (10 microM) enhanced the response to both bradykinin and FMLP. Bradykinin transiently activated rhythmic contractions in the isolated ureter. The response to bradykinin was blocked by HOE 140 and was unaffected by in vitro capsaicin desensitization, indomethacin, MEN 10,376 or BPLPLP. FMLP had no motor effect on the resting ureter but when rhythmic background contractions were evoked by the addition of 100 nM endothelin 1, it produced a transient suppression of ureteral motility. This inhibitory effect was unchanged by in vitro capsaicin desensitization or HOE 140 while it was abolished by indomethacin or BPLPLP pretreatment. Both bradykinin and FMLP evoked the release of CGRP-like immunoreactivity in the renal pelvis. The effect of bradykinin but not that of FMLP was abolished by indomethacin. By contrast neither bradykinin nor FMLP did evoke a significant CGRP-LI release in the ureter. It is concluded that bradykinin and FMLP affect pyeloureteral motility through specific and independent pathways. The local motor responses produced by these chemical stimulants are independent from the release of sensory neuropeptides from capsaicin-sensitive primary afferent neurons. Direct neurochemical evidence was obtained for activation of capsaicin-sensitive primary afferents in the renal pelvis: such a mechanism could be involved in the genesis of ureteral pain whenever bradykinin or FMLP come into contact with sensory nerves in the pyeloureteral wall.
在豚鼠离体肾盂和输尿管中，研究了缓激肽和细菌趋化肽甲酰甲硫氨酰亮氨酰苯丙氨酸（FMLP）的局部运动反应，以及与辣椒素敏感的初级传入神经可能的激活和感觉神经肽释放的关系。缓激肽（1 nM - 10 μM）和FMLP（10 nM - 10 μM）在离体肾盂中均产生浓度依赖性正性肌力作用，且不受体外辣椒素脱敏的影响。缓激肽的反应被缓激肽受体拮抗剂HOE 140拮抗，而速激肽受体拮抗剂MEN 10,376、降钙素基因相关肽（CGRP）受体拮抗剂hCGRP(8 - 37)和FMLP拮抗剂N - t - BOC - Phe - DLeu - Phe - DLeu - Phe（BPLPLP）对其无影响。FMLP的反应被BPLPLP阻断，而HOE 140、MEN 10,376或hCGRP(8 - 37)对其无影响。吲哚美辛（10 μM）增强了对缓激肽和FMLP的反应。缓激肽可短暂激活离体输尿管的节律性收缩。缓激肽的反应被HOE 140阻断，且不受体外辣椒素脱敏、吲哚美辛、MEN 10,376或BPLPLP的影响。FMLP对静息输尿管无运动作用，但当加入100 nM内皮素1诱发节律性背景收缩时，它会短暂抑制输尿管运动。这种抑制作用不受体外辣椒素脱敏或HOE 140的影响，而吲哚美辛或BPLPLP预处理可消除该作用。缓激肽和FMLP均可诱发肾盂中CGRP样免疫反应性的释放。吲哚美辛可消除缓激肽的作用，但不能消除FMLP的作用。相比之下，缓激肽和FMLP均未在输尿管中诱发显著的CGRP - LI释放。结论是，缓激肽和FMLP通过特定且独立的途径影响肾盂输尿管运动。这些化学刺激物产生的局部运动反应独立于辣椒素敏感的初级传入神经元释放感觉神经肽。获得了肾盂中辣椒素敏感的初级传入神经激活的直接神经化学证据：当缓激肽或FMLP与肾盂输尿管壁中的感觉神经接触时，这种机制可能参与输尿管疼痛的发生。
