Korolkiewicz R, Sliwiński W, Konstański Z, Rekowski P, Halama-Borowiec A, Szyk A, Emerich J, Korolkiewicz K Z
Department of Pharmacology, Medical University of Gdansk, Gdansk-Wrzeszcz, Poland.
Fundam Clin Pharmacol. 1997;11(6):576-83. doi: 10.1111/j.1472-8206.1997.tb00863.x.
Porcine galanin (1-29)-NH2, galantide (M15) and galanin (1-14)-(alpha-aminobutyric acid8)-scyliorhinin-I used in concentrations of 300, 1,000 and 3,000 nM respectively caused contractions of rat fundus strips. The contractile responses to galanin(1-29)-NH2 were not modified by atropine (10 microM), guanethidine (10 microM), naloxone (1 microM), a mixture of propranolol (10 microM) and phentolamine (10 microM), indomethacin (10 microM), a mixture of mepyramine (10 microM) and cimetidine (10 microM), saralasin (10 microM), and spantide (100 microM). The effects of M15 and galanin(1-14)-(alpha-aminobutyric acid8)-scyliorhinin-I were significantly decreased by atropine for 36 and 18% and by spantide for 37 and 26% respectively. Indomethacin inhibited the muscle response to M15 without influence on the galanin (1-14)-(alpha-aminobutyric acid8)-scyliorhinin-I-induced action. These results support findings that galanin (1-29)-NH2 contracts rat gastric fundus strips by stimulating specific receptors localized on the surface of smooth muscle cells. M15 and galanin(1-14)-(alpha-aminobutyric acid8)-scyliorhinin-I seem to contract smooth muscles not only by acting at galanin receptors, but by interacting with muscarinic or tachykinin receptors or modulating the release of acetylcholine and substance P. Diltiazem (EC50 825 nM), dantrolene (EC50 30.2 microM) and the phospholipase C inhibitors U-73122 (EC50 549 microM) and U-73343 (EC50 751 microM) lowered the contraction to galanin(1-29)-NH2 in a concentration-dependent manner. These observations imply that though the extracellular Ca2+ influx plays a major role in the action of galanin(1-29)-NH2, the release of Ca2+ ions from the intracellular stores contributes to the response of smooth muscles of galanin(1-29) NH2. Norepinephrine (30, 60, 100 and 300 nM) concentration-dependently reduced the Emax to galanin (1-29)-NH2 and reduced the slopes of the concentration-contraction curves, without a notable change in EC50. Pertussis toxin pre-treatment (10 and 30 mg/kg intravenous [i.v.]), 120 h before the experiment, notably increased the maximal response of the rat gastric fundus to galanin(1-29)-NH2, without a significant change in the properties of the concentration-contraction curves (EC50, slopes). The observations may suggest that pertussis toxin-sensitive GTP-binding proteins are involved in the modulation of the excitatory effects of galanin(1-29)-NH2 in the rat gastric fundus.
分别以300、1000和3000 nM的浓度使用的猪甘丙肽（1 - 29）- NH₂、甘丙肽拮抗剂（M15）和甘丙肽（1 - 14）-（α - 氨基丁酸⁸）- 鲨肌肽 - I可引起大鼠胃底条收缩。对甘丙肽（1 - 29）- NH₂的收缩反应不受阿托品（10 μM）、胍乙啶（10 μM）、纳洛酮（1 μM）、普萘洛尔（10 μM）和酚妥拉明（10 μM）的混合物、吲哚美辛（10 μM）、美吡拉敏（10 μM）和西咪替丁（10 μM）的混合物、沙拉新（10 μM）以及斯帕替啶（100 μM）的影响。M15和甘丙肽（1 - 14）-（α - 氨基丁酸⁸）- 鲨肌肽 - I的作用分别被阿托品显著降低36%和18%，被斯帕替啶显著降低37%和26%。吲哚美辛抑制了对M15的肌肉反应，而对甘丙肽（1 - 14）-（α - 氨基丁酸⁸）- 鲨肌肽 - I诱导的作用无影响。这些结果支持以下发现：甘丙肽（1 - 29）- NH₂通过刺激位于平滑肌细胞表面的特定受体使大鼠胃底条收缩。M15和甘丙肽（1 - 14）-（α - 氨基丁酸⁸）- 鲨肌肽 - I似乎不仅通过作用于甘丙肽受体使平滑肌收缩，还通过与毒蕈碱或速激肽受体相互作用或调节乙酰胆碱和P物质的释放来实现。地尔硫䓬（EC₅₀ 825 nM）、丹曲林（EC₅₀ 30.2 μM）以及磷脂酶C抑制剂U - 73122（EC₅₀ 549 μM）和U - 73343（EC₅₀ 751 μM）以浓度依赖性方式降低了对甘丙肽（1 - 29）- NH₂的收缩作用。这些观察结果表明，尽管细胞外Ca²⁺内流在甘丙肽（1 - 29）- NH₂的作用中起主要作用，但细胞内钙库中Ca²⁺离子的释放也有助于甘丙肽（1 - 29）- NH₂对平滑肌的反应。去甲肾上腺素（30、60、100和300 nM）以浓度依赖性方式降低了对甘丙肽（1 - 29）- NH₂的最大效应（Emax）并降低了浓度 - 收缩曲线的斜率，而EC₅₀无明显变化。在实验前120小时进行百日咳毒素预处理（静脉注射10和30 mg/kg）显著增加了大鼠胃底对甘丙肽（1 - 29）- NH₂的最大反应，而浓度 - 收缩曲线的特性（EC₅₀、斜率）无显著变化。这些观察结果可能表明百日咳毒素敏感的GTP结合蛋白参与了对甘丙肽（1 - 29）- NH₂在大鼠胃底的兴奋作用的调节。
