豚鼠膀胱中通过乙酰胆碱和γ-氨基丁酸释放对P物质诱导收缩的调节

Regulation of the substance P-induced contraction via the release of acetylcholine and gamma-aminobutyric acid in the guinea-pig urinary bladder.

作者信息

Shirakawa J, Nakanishi T, Taniyama K, Kamidono S, Tanaka C

机构信息

Department of Pharmacology, Kobe University, School of Medicine, Japan.

出版信息

Br J Pharmacol. 1989 Oct;98(2):437-44. doi: 10.1111/j.1476-5381.1989.tb12615.x.

DOI:10.1111/j.1476-5381.1989.tb12615.x

PMID:2479440

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1854731/

Abstract

The action of substance P (SP) on the release of gamma-aminobutyric acid (GABA) and acetylcholine (ACh) and on contraction were studied in strips of the guinea-pig urinary bladder. Substance P induced a dose-dependent contraction of strips of guinea-pig urinary bladder (EC50 = 1.2 x 10(-9) M). This contraction was not altered by tetrodotoxin, but with a dose of 10(-9) M and less, there was a complete inhibition by 10(-6) M) atropine. Contractions initiated by 3 x 10(-9) M) SP or more were partly inhibited by atropine. The EC50 value of substance P in the presence of atropine was 7.0 x 10(-9) M. 2. Substance P induced a Ca2+-dependent and tetrodotoxin-resistant release of [3H]-acetylcholine (ACh) from strips of urinary bladder preloaded with [3H]-choline (EC50 = 4.9 x 10(-10) M), and this release was antagonized by [D-Pro2,D-Trp7,9] substance P. 3. Bicuculline increased the substance P-induced contraction and the release of [3H]-ACh from the strips. 4. Substance P induced a Ca2+-dependent and tetrodotoxin-sensitive release of [3H]-gamma-aminobutyric acid (GABA) from strips preloaded with [3H]-GABA (EC50 = 2.6 x 10(-9) M), and this release was antagonized by [D-Pro2,D-Trp7,9] substance P. 5. Therefore, substance P appears to exert excitatory effects on the contractility of urinary bladder predominantly by stimulating its own receptor located on the cholinergic nerve terminals. GABA released by substance P inhibits stimulation of the cholinergic neurone. However, the direct action of substance P on the cholinergic neurone is more potent that the indirect action via GABA release.

摘要

研究了P物质（SP）对豚鼠膀胱条中γ-氨基丁酸（GABA）和乙酰胆碱（ACh）释放及收缩的作用。P物质可引起豚鼠膀胱条剂量依赖性收缩（半数有效浓度[EC50]=1.2×10⁻⁹ M）。这种收缩不受河豚毒素影响，但在剂量为10⁻⁹ M及以下时，10⁻⁶ M阿托品可完全抑制。由3×10⁻⁹ M SP或更高剂量引发的收缩部分受阿托品抑制。存在阿托品时P物质的EC50值为7.0×10⁻⁹ M。2. P物质可引起预先用[³H] - 胆碱加载的膀胱条释放[³H] - 乙酰胆碱（ACh），这种释放依赖于Ca²⁺且对河豚毒素不敏感（EC50 = 4.9×10⁻¹⁰ M），且这种释放被[D - Pro²，D - Trp⁷,⁹]P物质拮抗。3. 荷包牡丹碱增加了P物质诱导的收缩以及膀胱条中[³H] - ACh的释放。4. P物质可引起预先用[³H] - GABA加载的膀胱条释放[³H] - γ-氨基丁酸（GABA），这种释放依赖于Ca²⁺且对河豚毒素敏感（EC50 = 2.6×10⁻⁹ M），且这种释放被[D - Pro²，D - Trp⁷,⁹]P物质拮抗。5. 因此，P物质似乎主要通过刺激位于胆碱能神经末梢上的自身受体，对膀胱收缩力发挥兴奋作用。P物质释放的GABA抑制胆碱能神经元的刺激。然而，P物质对胆碱能神经元的直接作用比通过GABA释放的间接作用更强。