肌醇三磷酸（InsP3）而非新型钙离子释放剂，参与介导兔气道平滑肌中激动剂引发的收缩。

InsP3, but not novel Ca2+ releasers, contributes to agonist-initiated contraction in rabbit airway smooth muscle.

作者信息

Iizuka K, Yoshii A, Dobashi K, Horie T, Mori M, Nakazawa T

机构信息

First Department of Internal Medicine, Gunma University Faculty of Medicine, School of Medicine, Gunma, Japan.

出版信息

J Physiol. 1998 Sep 15;511 ( Pt 3)(Pt 3):915-33. doi: 10.1111/j.1469-7793.1998.915bg.x.

DOI:10.1111/j.1469-7793.1998.915bg.x

PMID:9714870

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2231150/

Abstract

To examine the contributions of the putative Ca2+ releasers, inositol 1,4,5-trisphosphate (InsP3), cyclic ADP ribose (cADPR), and nicotinate adenine dinucleotide phosphate (NAADP), to carbachol (CCh)-induced contraction in airway smooth muscle, we measured force development of permeabilized rabbit tracheal smooth muscle, human bronchial smooth muscle and guinea-pig ileum longitudinal smooth muscle. 2. In the presence of 50 microM GTP, CCh and InsP3 contracted alpha-toxin-permeabilized tracheal smooth muscle dose dependently; the EC50 values for CCh and InsP3 were 1.84 microM and 363 microM, and the maximum responses (normalized to the 30 mM caffeine response) to 100 microM CCh and to 800 microM InsP3 were 206 +/- 13.4 % (mean +/- S.E.M.) and 84.4 +/- 5.3 %, respectively. 3. However, cADPR (10-300 microM), beta-NAD+ (2.5 mM), FK506 (30 microM) and NAADP (100 microM) neither contracted the strip by themselves nor affected the subsequent CCh (1 microM) response. alpha-Toxin-permeabilized bronchial smooth muscle and ileum smooth muscle also responded to caffeine, InsP3 and CCh but not to cADPR. 4. Both 100 microM 8-amino-cADPR, a selective cADPR antagonist, and 100 microM thionicotinamide-NADP, a selective NAADP antagonist, failed to inhibit the CCh response, although procaine abolished the caffeine, InsP3 and CCh responses in the permeabilized tracheal smooth muscle. 5. Although inhibition of the caffeine response by 30 microM ryanodine was nearly complete, approximately 30 % of the InsP3 (300 microM) plus GTP (50 microM) response was retained, and the resultant response disappeared after the caffeine response was evoked in the presence of ryanodine. 6. Heparin (300 microg ml-1) blocked InsP3 (300 microM) and CCh (3 microM) responses in beta-escin-permeabilized tracheal smooth muscle, while Ruthenium Red (100 microM) partially inhibited the CCh response. 7. Collectively, InsP3 but not cADPR or NAADP plays a key role in CCh-initiated contraction, and InsP3 utilizes a single compartment of the caffeine/ryanodine-sensitive stored Ca2+ in airway smooth muscle.

摘要

为了研究假定的钙离子释放剂肌醇1,4,5 - 三磷酸（InsP3）、环ADP核糖（cADPR）和烟酰胺腺嘌呤二核苷酸磷酸（NAADP）对气道平滑肌中卡巴胆碱（CCh）诱导收缩的作用，我们测量了经通透处理的兔气管平滑肌、人支气管平滑肌和豚鼠回肠纵行平滑肌的张力变化。2. 在存在50微摩尔GTP的情况下，CCh和InsP3能剂量依赖性地使α - 毒素通透处理的气管平滑肌收缩；CCh和InsP3的半数有效浓度（EC50）值分别为1.84微摩尔和363微摩尔，100微摩尔CCh和800微摩尔InsP3的最大反应（相对于30毫摩尔咖啡因反应进行归一化）分别为206±13.4%（平均值±标准误）和84.4±5.3%。3. 然而，cADPR（10 - 300微摩尔）、β - NAD⁺（2.5毫摩尔）、FK506（30微摩尔）和NAADP（100微摩尔）自身均不能使肌条收缩，也不影响随后的CCh（1微摩尔）反应。α - 毒素通透处理的支气管平滑肌和回肠平滑肌对咖啡因、InsP3和CCh有反应，但对cADPR无反应。4. 100微摩尔的8 - 氨基 - cADPR（一种选择性cADPR拮抗剂）和100微摩尔的硫代烟酰胺 - NADP（一种选择性NAADP拮抗剂）均未能抑制CCh反应，尽管普鲁卡因可消除通透处理的气管平滑肌中咖啡因、InsP3和CCh的反应。5. 虽然30微摩尔的ryanodine对咖啡因反应的抑制几乎是完全的，但InsP3（300微摩尔）加GTP（50微摩尔）反应仍保留约30%，并且在ryanodine存在下诱发咖啡因反应后，剩余反应消失。