最近の記事

2024/08/06
Validation of a new protocol for a zebrafish MEFL (malformation or embryo-fetal lethality) test method that conforms to the ICH S5 (R3) guideline.
2024/05/21
In vivo assessment of individual and total proteinuria in zebrafish larvae using the solvatochromic compound ZMB741
2021/10/31
Generation of a Transgenic Zebrafish Line for In Vivo Assessment of Hepatic Apoptosis
2021/08/19
Patient-Derived Cancer Xenograft Zebrafish Model (PDXZ) for Drug Discovery Screening and Personalized Medicine
2021/07/09
Establishment of a Quality Control Protocol for Zebrafish Developmental Toxicity Studies
2020/10/13
Gap junction protein beta 4 plays an important role in cardiac function in humans, rodents, and zebrafish
2020/05/28
A novel orexin antagonist from a natural plant was discovered using zebrafish behavioural analysis
2019/10/15
C3orf70 Is Involved in Neural and Neurobehavioral Development
2019/09/22
Generation of a Triple-Transgenic Zebrafish Line for Assessment of Developmental Neurotoxicity during Neuronal Differentiation
2019/07/17
Aging-associated microstructural deterioration of vertebra in 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