豚鼠膀胱在体外和体内对ATP诱导收缩的抑制作用。

Inhibition of ATP-induced contraction in the guinea-pig urinary bladder in vitro and in vivo.

作者信息

Sjögren C, Andersson K E

出版信息

Acta Pharmacol Toxicol (Copenh). 1979 Mar;44(3):221-7. doi: 10.1111/j.1600-0773.1979.tb02321.x.

DOI:10.1111/j.1600-0773.1979.tb02321.x

Abstract

Contractions were elicted by adenosine 5'-triphosphate (ATP) in the guinea-pig urinary bladder in vitro and in vivo. In isolated detrusor strips, tetrodotoxin (3.1 x 10(-6)--4.4 x 10(-5) M) did not affect contractions induced by a submaximum concentration (10(-3) M) of ATP, nor did atropine (1.7 X 10(-6)--2.1 x 10(-4) M), or the anticholinergic agent PR 197 within the concentration range 2.6 x 10(-8)--2.6 x (0(-5) M. In higher concentractions (5.2 x 10(-5)--2.6 x 10(-4) M), PR 197 inhibited the ATP-response by 60-70% in a way that was not clearly concentration-related. Isoprenaline (10(-7)--2.0 x 10(-5) M) and noradrenaline (2.5 x 10(-6)--10(-4) M) reduced the ATP-induced contractions by up to 79%. The effects of the amines were abolished by propranolol (5.2 x 10(-6)--3.8 x 10(-5) M). Adenosine, 1.0--2.0 x 10(-2) M, reduced the ATP-response by about 50%; in lower concentrations, it had no effect. Nifedipine, 7.8 x 10(-7)--1.2 x 10(-5) M, reduced the responses by 15-79%. Indomethacin (less than 2.0 x 10(-4) M), and theophylline (2.0 x 10(-4) M) had no consistent effects on ATP-induced concentrations. Exposure of the preparations to a calcium-free medium reduced and abolished the ATP-response within 60 min. Intravenous injection of ATP (1-20 MG/KG) caused a rapid and transient increase in intravesical pressure in the anaesthetized guinea-pig. The effect of ATP (3 mg/kg) was reduced by atropine (5-10 mg/kg) by approximately 35%. PR 197 (2.5-5 mg/kg) abolished the ATP-response. Isoprenaline (5-100 microgram/kg) caused a 53-95% inhibition that could be blocked by propranolol (1 mg/kg). The inhibiting effect of noradrenaline (10-100 microgram/kg) could not be blocked by propranolol (1 mg/kg). Adenosine (1.5-3.0 mg/kg) given immedicately before ATP completely inhibited the ATP-response. Nifedipine, 0.1-0.2 mg/kg, reduced the ATP-induced contraction by 34 to 100%. It is concluded that the ATP-induced contraction is elicted by a direct effect on the smooth muscle cell. It can be inhibited non-specifically by drugs with different modes of action.

摘要

在豚鼠膀胱体外和体内实验中，通过5'-三磷酸腺苷（ATP）引发收缩。在离体逼尿肌条中，河豚毒素（3.1×10⁻⁶ - 4.4×10⁻⁵ M）不影响由次最大浓度（10⁻³ M）的ATP诱导的收缩，阿托品（1.7×10⁻⁶ - 2.1×10⁻⁴ M）以及抗胆碱能药物PR 197在2.6×10⁻⁸ - 2.6×10⁻⁵ M浓度范围内也无影响。在较高浓度（5.2×10⁻⁵ - 2.6×10⁻⁴ M）时，PR 197以一种与浓度无明显相关性的方式使ATP反应抑制60 - 70%。异丙肾上腺素（10⁻⁷ - 2.0×10⁻⁵ M）和去甲肾上腺素（2.5×10⁻⁶ - 10⁻⁴ M）使ATP诱导的收缩减少高达79%。普萘洛尔（5.2×10⁻⁶ - 3.8×10⁻⁵ M）可消除胺类药物的作用。1.0 - 2.0×10⁻² M的腺苷使ATP反应降低约50%；在较低浓度时无作用。硝苯地平（7.8×10⁻⁷ - 1.2×10⁻⁵ M）使反应降低15 - 79%。吲哚美辛（小于2.0×10⁻⁴ M）和茶碱（2.0×10⁻⁴ M）对ATP诱导的收缩无一致影响。将标本置于无钙培养基中60分钟内可使ATP反应降低并消除。静脉注射ATP（1 - 20毫克/千克）可使麻醉豚鼠膀胱内压迅速短暂升高。ATP（3毫克/千克）的作用可被阿托品（5 - 10毫克/千克）降低约35%。PR 197（2.5 - 5毫克/千克）可消除ATP反应。异丙肾上腺素（5 - 100微克/千克）可产生53 - 95%的抑制作用，普萘洛尔（1毫克/千克）可阻断该作用。去甲肾上腺素（10 - 100微克/千克）的抑制作用不能被普萘洛尔（1毫克/千克）阻断。在ATP给药前立即给予腺苷（1.5 - 3.0毫克/千克）可完全抑制ATP反应。硝苯地平，0.1 - 0.2毫克/千克，使ATP诱导的收缩降低34%至100%。结论是，ATP诱导的收缩是通过对平滑肌细胞的直接作用引发的。它可被具有不同作用方式的药物非特异性抑制。