最近の記事

2019/02/18
Toxicological Evaluation of SiO2 Nanoparticles by Zebrafish Embryo Toxicity Test
2018/12/27
Increased susceptibility to oxidative stress-induced toxicological evaluation by genetically modified nrf2a-deficient zebrafish.
2018/01/18
EGF receptor kinase suppresses ciliogenesis through activation of USP8 deubiquitinase
2017/11/23
Chemokines protect vascular smooth muscle cells from cell death induced by cyclic mechanical stretch.
2017/07/29
New photic stimulating system with white light-emitting diodes to elicit electroretinograms from zebrafish larvae.
2017/03/09
Potential protective function of the sterol regulatory element binding factor 1-fatty acid desaturase 12 axis in early-stage age-related macular degeneration
2016/07/11
Activation of Sterol Regulatory Element Binding Factors by Fenofibrate and Gemfibrozil Stimulates Myelination in Zebrafish
2016/06/14
Downregulation of GSTK1 Is a Common Mechanism Underlying Hypertrophic Cardiomyopathy
2016/06/07
Comparative Transcriptome Analysis Identifies CCDC80 as a Novel Gene Associated with Pulmonary Arterial Hypertension
2016/06/06
Establishment of a drug evaluation model against light-induced retinal degeneration using adult pigmented zebrafish

一覧に戻る

1986/03/29
  • CiteULike
  • reddit
  • StumbleUpon
  • linkedin
  • Delicious
  • Mendeley
  • はてなブックマーク
  • Youtube
  • Google+
  • Twitter
  • Facebook

Modulation of calmodulin function and of Ca2+-induced smooth muscle contraction by the calmodulin antagonist, HT-74.

Tanaka T, Umekawa H, Saitoh M, Ishikawa T, Shin T, Ito M, Itoh H, Kawamatsu Y, Sugihara H, Hidaka H.
Mol Pharmacol. 1986 Mar;29(3):264-9.

Abstract

The relationship between the functions of calmodulin (CaM) and Ca2+-induced smooth muscle contraction was investigated using a newly synthesized CaM antagonist, 3-(2-benzothiazolyl)-4,5-dimethoxy-N-[3-(4- -phenylpiperidinyl)propyl]benzenesulfonamide (HT-74). We noted a selectivity of HT-74 for CaM, compared to other calcium-binding proteins and target enzymes of CaM. As HT-74 had no significant effect on the intensity of 8-anilino-1-naphthalene-sulfonic acid (ANS) fluorescence in the presence of the Ca2+-CaM complex, the HT-74-binding sites may differ from those of naphthalenesulfonamides and phenothiazines which decrease ANS fluorescence. The Ca2+ binding to CaM was inhibited significantly by 1.0 microM HT-74, in sharp contrast to phenothiazines and naphthalenesulfonamides which increase the extent of the Ca2+ binding to CaM. Increasing CaM concentrations reversed the HT-74-induced inhibition of CaM-dependent enzymes such as myosin light chain kinase and Ca2+-dependent cyclic nucleotide phosphodiesterase, with Ki values of 0.5 microM and 0.4 microM, respectively. In the presence of 0.3 microM HT-74, potassium-depolarized rabbit aortic strips pre-contracted with 0.3 mM CaCl2 relaxed, and this relaxation was completely reversed by the addition of an excess amount of CaCl2 (10 mM). This compound shifted the dose-response curve for CaCl2 to the right, in a competitive manner. However, HT-74 inhibited the phenylephrine-induced contraction elicited in Ca2+-free solution and the calcium ionophore A23187-induced contraction in the presence of calcium ion. Therefore, this agent affects intracellular actions of Ca2+ rather than membrane receptors or the influx of Ca2+. HT-74 is a CaM antagonist which binds to CaM in a manner different from that heretofore reported. It inhibits Ca2+ binding to CaM and produces a competitive inhibition of Ca2+-induced contractions of depolarized vascular smooth muscle.

関連リンク