Maggi C A, Santicioli P, Patacchini R, Geppetti P, Giuliani S, Astolfi G M, Baldi E, Parlani M, Theodorsson E, Fusco B
Pharmacology Department, A. Menarini Pharmaceuticals, Florence, Italy.
Neuroscience. 1988 Nov;27(2):675-88. doi: 10.1016/0306-4522(88)90297-7.
Capsaicin induced a contraction of isolated strips from the guinea-pig urinary bladder which was more evident in the dome than in the neck and inhibited contractions induced by field stimulation, particularly in the neck. Both responses exhibited prompt desensitization and were tetrodotoxin-resistant, suggesting a specific action on transmitter release from sensory nerve terminals. Indeed, the contractile response in the dome was prevented by a substance P antagonist while the inhibitory response in the neck was prevented by immunoblockade with anticalcitonin gene-related peptide (CGRP) serum. Substance P produced a contraction of the guinea-pig bladder, being about 5 times more potent in the dome than in the neck, while CGRP inhibited the evoked contractions, being about 8 times more potent in the neck than in the dome. Further, the maximal effect of CGRP in the neck was almost double that in the dome. Substance P- and CGRP-like immunoreactivity were detected in both the dome and the neck with no regional differences for each peptide. CGRP-like immunoreactivity was 6.3 and 7.9 times higher than substance P-like immunoreactivity in the dome and the neck, respectively. Exposure to capsaicin evoked release of both substance P- and CGRP-like immunoreactivity from the dome and the neck. Peak CGRP-like immunoreactivity released by capsaicin was 12.3 and 8 times greater than substance P-like immunoreactivity in the dome and the neck, respectively. For each peptide, no difference was found in peak release in the dome vs neck. Total substance P-like immunoreactivity released from the neck was 25% lower than that released from the dome. The ability of CGRP to stimulate accumulation of 3',5' cyclic adenosine monophosphate in membranes prepared from the bladder muscle was greater in preparations from the neck than from the dome. These findings indicate that postjunctional mechanisms (type and number of receptors for sensory neuropeptides, coupling with second messengers) are a major determinant of the type of motor responses consequent of the release of sensory neuropeptides from capsaicin-sensitive nerves.
辣椒素可引起豚鼠膀胱离体肌条收缩，这种收缩在膀胱顶部比颈部更明显，并且可抑制电场刺激诱导的收缩，尤其是在颈部。这两种反应均表现出快速脱敏且对河豚毒素不敏感，提示其对感觉神经末梢递质释放具有特异性作用。实际上，膀胱顶部的收缩反应可被P物质拮抗剂阻断，而颈部的抑制反应可被抗降钙素基因相关肽（CGRP）血清免疫阻断。P物质可引起豚鼠膀胱收缩，在膀胱顶部的效力约为颈部的5倍，而CGRP可抑制诱发的收缩，在颈部的效力约为膀胱顶部的8倍。此外，CGRP在颈部的最大效应几乎是膀胱顶部的两倍。在膀胱顶部和颈部均检测到P物质和CGRP样免疫反应性，每种肽均无区域差异。膀胱顶部和颈部的CGRP样免疫反应性分别比P物质样免疫反应性高6.3倍和7.9倍。暴露于辣椒素可引起膀胱顶部和颈部释放P物质和CGRP样免疫反应性。辣椒素释放的CGRP样免疫反应性峰值在膀胱顶部和颈部分别比P物质样免疫反应性高12.3倍和8倍。对于每种肽，膀胱顶部和颈部的峰值释放无差异。从颈部释放的总P物质样免疫反应性比从膀胱顶部释放的低25%。CGRP刺激膀胱肌肉制备膜中3',5'环磷酸腺苷积累的能力在颈部制备物中比在膀胱顶部制备物中更强。这些发现表明，接头后机制（感觉神经肽的受体类型和数量、与第二信使的偶联）是辣椒素敏感神经释放感觉神经肽后运动反应类型的主要决定因素。
