可溶性和颗粒性鸟苷酸环化酶激活对牛气管平滑肌中环鸟苷酸升高及舒张的比较效应。

Comparative effects of activation of soluble and particulate guanylyl cyclase on cyclic GMP elevation and relaxation of bovine tracheal smooth muscle.

作者信息

Ijioma S C, Challiss R A, Boyle J P

机构信息

Department of Cell Physiology & Pharmacology, University of Leicester.

出版信息

Br J Pharmacol. 1995 Jul;115(5):723-32. doi: 10.1111/j.1476-5381.1995.tb14993.x.

DOI:10.1111/j.1476-5381.1995.tb14993.x

PMID:8548169

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1908512/

Abstract

The effects of nitric oxide-donating compounds and atrial natriuretic peptide on cyclic GMP accumulation and mechanical tone were compared with the effects of isoprenaline in bovine tracheal smooth muscle. 2. Sodium nitroprusside, glyceryl trinitrate, S-nitroso-N-acetylpenicillamine (SNAP), atrial natriuretic peptide and isoprenaline each caused concentration-dependent inhibitions of histamine-maintained tone (EC50 values 320 +/- 80, 150 +/- 45, 14,000 +/- 4,000, 2.8 +/- 0.8 and 6.6 +/- 4.3 nM respectively). 3. When compared with their effects on histamine-induced tone, sodium nitroprusside was equally potent and effective in causing relaxation of methacholine-supported tone (EC50 290 +/- 90 nM) while isoprenaline was as effective, but less potent (EC50 30 +/- 7 nM). SNAP was more potent and equi-effective as a relaxant of methacholine-supported tone (EC50 340 +/- 140 nM). At the maximum concentrations of glyceryl trinitrate and atrial natriuretic peptide tested against methacholine-supported tone, relaxations of 52% and 14% of the isoprenaline maximum were seen. 4. Sodium nitroprusside, glyceryl trinitrate and atrial natriuretic peptide each induced concentration-dependent increases in cyclic GMP accumulation. The time-courses of accumulation correlated closely with the relaxant actions of these compounds. 5. Pretreatment of tracheal smooth muscle with sodium nitroprusside or SNAP caused a rightward shift of the concentration-effect curve for histamine while reducing the maximum response. 6. LY 83583, a putative guanylyl cyclase inhibitor, caused a concentration-dependent reduction in basal cyclic GMP accumulation in tracheal smooth muscle and inhibited the effects of sodium nitroprusside on cyclic GMP accumulation. 7. LY 83583 also inhibited the relaxation of histamine-supported tone by glyceryl trinitrate, sodium nitroprusside, SNAP and atrial natriuretic peptide, and also sodium nitroprusside- and SNAP-induced relaxation of methacholine-supported tone. However, it had no significant effect on glyceryl trinitrate-induced relaxation of methacholine-supported tone. 8. It is concluded that the relaxant actions of sodium nitroprusside, glyceryl trinitrate, SNAP and atrial natriuretic peptide follow as a result of their ability to activate either soluble or particulate guanylyl cyclase leading to cyclic GMP accumulation. Although there does not seem to be any functional difference in the relaxant response to cyclic GMP generated by the particulate as opposed to soluble form(s) of guanylyl cyclase, atrial natriuretic peptide receptor/guanylyl cyclase activation was much less effective in causing relaxation of methacholine-supported tone when compared to activators of soluble guanylyl cyclase.

摘要

将一氧化氮供体化合物和心房利钠肽对环磷酸鸟苷（cGMP）积累及肌张力的影响与异丙肾上腺素在牛气管平滑肌中的作用进行了比较。2. 硝普钠、硝酸甘油、S-亚硝基-N-乙酰青霉胺（SNAP）、心房利钠肽和异丙肾上腺素均引起组胺维持张力的浓度依赖性抑制（EC50值分别为320±80、150±45、14000±4000、2.8±0.8和6.6±4.3 nM）。3. 与它们对组胺诱导张力的作用相比，硝普钠在引起乙酰甲胆碱维持张力的松弛方面同样有效且效力相当（EC50 290±90 nM），而异丙肾上腺素同样有效但效力较低（EC50 30±7 nM）。SNAP作为乙酰甲胆碱维持张力的松弛剂更有效力且效力相当（EC50 340±140 nM）。在针对乙酰甲胆碱维持张力测试的硝酸甘油和心房利钠肽的最大浓度下，观察到的松弛分别为异丙肾上腺素最大松弛的52%和14%。4. 硝普钠、硝酸甘油和心房利钠肽各自诱导cGMP积累的浓度依赖性增加。积累的时间进程与这些化合物的松弛作用密切相关。5. 用硝普钠或SNAP预处理气管平滑肌导致组胺浓度 - 效应曲线右移，同时降低最大反应。6. LY 83583，一种假定的鸟苷酸环化酶抑制剂，导致气管平滑肌基础cGMP积累的浓度依赖性降低，并抑制硝普钠对cGMP积累的作用。7. LY 83583还抑制硝酸甘油、硝普钠、SNAP和心房利钠肽对组胺维持张力的松弛作用，以及硝普钠和SNAP诱导的乙酰甲胆碱维持张力的松弛作用。然而，它对硝酸甘油诱导的乙酰甲胆碱维持张力的松弛作用无显著影响。8. 得出结论，硝普钠、硝酸甘油、SNAP和心房利钠肽的松弛作用是由于它们激活可溶性或颗粒性鸟苷酸环化酶导致cGMP积累的能力。尽管对于颗粒性与可溶性形式的鸟苷酸环化酶产生的环磷酸鸟苷的松弛反应似乎没有任何功能差异，但与可溶性鸟苷酸环化酶激活剂相比，心房利钠肽受体/鸟苷酸环化酶激活在引起乙酰甲胆碱维持张力的松弛方面效果要差得多。