Hua X Y, Theodorsson-Norheim E, Lundberg J M, Kinn A C, Hökfelt T, Cuello A C
Department of Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Neuroscience. 1987 Nov;23(2):693-703.
Tachykinin- and calcitonin gene-related peptide (CGRP) immunoreactivities were localized by immunohistochemistry in the same nerves of the kidney, renal pelvis and ureter as well as in spinal ganglion cells of both the guinea-pig and man. The tachykinin and CGRP-immunoreactive nerves in the ureter were present within the smooth muscle layers, around blood vessels, close to and within the lining epithelium. The levels of neurokinin A-, substance P- and CGRP-like immunoreactivity per tissue weight, as determined by radioimmunoassay, were about 30-100-fold higher in the guinea-pig than in the human ureter, which was in good agreement with the relative density of immunoreactive nerve fibres, as seen by immunohistochemistry. Capsaicin treatment caused an almost total disappearance of both neurokinin A-, substance P- and CGRP-immunoreactive nerve fibres in the guinea-pig ureter and a 90% depletion of neurokinin A, substance P- and CGRP-like immunoreactivity, further supporting a sensory origin of these nerves. Reversed-phase high performance liquid chromatography of water extracts of the human ureter revealed the presence of neurokinin A- and eledoisin-like material using antiserum K12, which does not cross-react with substance P. Most of the CGRP-like immunoreactivity in human ureter extracts co-eluted with synthetic human CGRP. Capsaicin both caused inhibition of spontaneous motility of the human ureter in vitro and initiated contractions in some preparations. Neurokinin A and neuropeptide K potently initiated phasic contractions of the ureter, while substance P had only minor contractile effects. CGRP inhibited both spontaneous and neurokinin A-induced ureteric contractions. In conclusion, peptides with potent opposite motility effects are present in the same, presumably sensory nerves of the ureter in both the guinea-pig and man. It will be of importance to determine whether local release of neuropeptides can account for ureteric motility changes accompanying sensory nerve activation upon ureteral obstruction, by e.g. renal calculi.
速激肽和降钙素基因相关肽（CGRP）免疫反应性通过免疫组织化学定位在豚鼠和人的肾脏、肾盂及输尿管的相同神经以及脊髓神经节细胞中。输尿管中的速激肽和CGRP免疫反应性神经存在于平滑肌层内、血管周围、靠近内衬上皮并在内衬上皮内。通过放射免疫测定法测定，每组织重量中神经激肽A、P物质和CGRP样免疫反应性的水平在豚鼠输尿管中比人输尿管中高约30 - 100倍，这与免疫组织化学所见的免疫反应性神经纤维的相对密度一致。辣椒素处理导致豚鼠输尿管中神经激肽A、P物质和CGRP免疫反应性神经纤维几乎完全消失，以及神经激肽A、P物质和CGRP样免疫反应性减少90%，进一步支持了这些神经的感觉起源。人输尿管水提取物的反相高效液相色谱显示，使用不与P物质交叉反应的抗血清K12，存在神经激肽A和类eledoisin物质。人输尿管提取物中的大多数CGRP样免疫反应性与合成人CGRP共洗脱。辣椒素在体外既抑制人输尿管的自发运动，又在一些制剂中引发收缩。神经激肽A和神经肽K有力地引发输尿管的相性收缩，而P物质只有轻微的收缩作用。CGRP抑制自发的和神经激肽A诱导的输尿管收缩。总之，在豚鼠和人的输尿管相同的、可能是感觉神经中存在具有强大相反运动效应的肽。确定神经肽的局部释放是否能解释输尿管梗阻（例如肾结石）时感觉神经激活伴随的输尿管运动变化将具有重要意义。
