阿托品对兔主动脉中去甲肾上腺素诱导收缩的抑制作用的可能机制。

Possible mechanisms of inhibition with atropine against noradrenaline-induced contraction in the rabbit aorta.

作者信息

Satake N, Kiyoto S, Shibata S, Gandhi V, Jones D J, Morikawa M

机构信息

Department of Pharmacology, University of Hawaii, School of Medicine, Honolulu 96822.

出版信息

Br J Pharmacol. 1992 Oct;107(2):553-8. doi: 10.1111/j.1476-5381.1992.tb12782.x.

DOI:10.1111/j.1476-5381.1992.tb12782.x

PMID:1330185

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1907863/

Abstract

In the rabbit isolated aorta, atropine (3 x 10(-6) M-10(-4) M) inhibited contractile response to noradrenaline without affecting contraction to KCl. 2. In the presence of contraction to noradrenaline, atropine (3 x 10(-7) M-10(-4) M) caused concentration-dependent relaxation. Pretreatment with theophylline (10(-3) M) potentiated the relaxant action of atropine. Relaxation to atropine was not affected by the specific guanosine 3':5'-cyclic monophosphate phosphodiesterase inhibitor, M & B 22,948 (10(-4) M), tetraethylammonium (10 mM), indomethacin (10(-5) M), propranolol (10(-7) M), nifedipine (10(-6) M) or removal of the endothelium. 3. Relaxation to either atropine or prazosin was not affected by preincubation with prazosin and atropine, respectively. 4. In Ca(2+)-free medium containing EGTA and nifedipine, atropine (10(-7) M-10(-4) M) inhibited the residual noradrenaline response more than the subsequent Ca(2+)-induced contraction. Pretreatment with either theophylline (10(-3) M), forskolin (3 x 10(-7) M) or a low concentration of prazosin (3 x 10(-9) M) also inhibited the residual contraction to noradrenaline and Ca2+. The effect of combined treatment of atropine and any of these agents was much greater than with each individual agent. 5. Atropine (10(-6) M-10(-4) M) also inhibited increases in the level of inositol monophosphates (IP) in response to noradrenaline. Theophylline (10(-3) M) and a low concentration of prazosin (3 x 10(-9) M) also inhibited IP formation. Combined with atropine, the effect was much greater than with each of these agents individually. 6. Atropine did not affect adenosine 3':5'-cyclic monophosphate (cyclic AMP) levels in the aorta and also failed to displace specific [3H]-prazosin binding.7. These results suggest the possibility that smooth muscle relaxation to atropine may be due to the inhibition of phosphoinositide metabolism. The relaxation is not apparently due to an action of atropine on ax-adrenoceptors, or a change in the level of cyclic AMP.

摘要

在兔离体主动脉中，阿托品（3×10⁻⁶M - 10⁻⁴M）抑制对去甲肾上腺素的收缩反应，而不影响对氯化钾的收缩反应。2. 在存在对去甲肾上腺素的收缩反应时，阿托品（3×10⁻⁷M - 10⁻⁴M）引起浓度依赖性舒张。用茶碱（10⁻³M）预处理可增强阿托品的舒张作用。对阿托品的舒张作用不受特异性鸟苷3':5'-环磷酸单酯磷酸二酯酶抑制剂M&B 22,948（10⁻⁴M）、四乙铵（10mM）、吲哚美辛（10⁻⁵M）、普萘洛尔（10⁻⁷M）、硝苯地平（10⁻⁶M）或去除内皮的影响。3. 分别用哌唑嗪和阿托品预孵育后，对阿托品或哌唑嗪的舒张作用无影响。4. 在含有乙二醇双乙醚二胺四乙酸（EGTA）和硝苯地平的无钙培养基中，阿托品（10⁻⁷M - 10⁻⁴M）对残余去甲肾上腺素反应的抑制作用大于随后钙诱导的收缩。用茶碱（10⁻³M）、福斯可林（3×10⁻⁷M）或低浓度哌唑嗪（3×10⁻⁹M）预处理也抑制对去甲肾上腺素和钙的残余收缩。阿托品与这些药物联合治疗的效果远大于单独使用每种药物的效果。5. 阿托品（10⁻⁶M - 10⁻⁴M）也抑制对去甲肾上腺素反应时肌醇单磷酸（IP）水平的升高。茶碱（10⁻³M）和低浓度哌唑嗪（3×10⁻⁹M）也抑制IP的形成。与阿托品联合使用时，效果远大于单独使用这些药物中的任何一种。6. 阿托品不影响主动脉中腺苷3':5'-环磷酸单酯（环磷酸腺苷）水平，也不能取代特异性[³H] - 哌唑嗪结合。7. 这些结果提示，平滑肌对阿托品舒张可能是由于抑制磷脂酰肌醇代谢。这种舒张显然不是由于阿托品对α - 肾上腺素能受体的作用或环磷酸腺苷水平的改变。