フォトスイッチブルマスカリンアゴニストによる心臓機能の光学制御

Fabio Riefolo^1,2, Carlo Matera^1,2, Aida Garrido-Charles^1,2

¹Institute for Bioengineering of Catalonia (IBEC) , Barcelona Institute for Science and Technology (BIST) , Carrer de Baldiri Reixac 15-21 , 08028 Barcelona , Spain.

Journal of the American Chemical Society

|April 24, 2019

まとめ

研究者は光で心臓の機能を制御する新しい光スイッチ可能な化合物 (PAI) を開発し遺伝子改変の必要性を回避しましたこの光で活性化される分子は非侵襲的なオンデマンドの心臓治療に新たな道を開きます

科学分野:

生物医学工学
心血管薬学
オプトジェネティクス

背景:

オプトジェネティクスは生理学的機能の正確な制御を提供しますが,臨床応用は遺伝的変異の要件によって制限されています.
心臓機能の光誘発調節のための非遺伝的方法の開発は,治療の進歩にとって極めて重要です.

研究の目的:

遺伝子操作なしに心臓機能の光に依存した調節のための新しい光スイッチ可能な化合物 (PAI) を提示する.
M2マスカリン・アセチルコリン受容体 (M2mAChRs) の活性化と心臓活動の制御におけるPAIの有効性を実証する.

主な方法:

M2 mAChRアゴニスト構造にフォトスイッチを組み込むことでPAIの設計.
PAIによって光に依存するM2 mAChRの活性化を確認するための in vitro 測定法.
哺乳類のモデルと半透明なタッドポールのin vivo検証で,心臓機能の光制御を証明する.

主要な成果:

PAIのフォトアイソマーは哺乳類のモデルで明確な心臓効果を示した.
逆戻り可能な,リアルタイムの心臓機能の写真制御がタドウで達成されました.
PAIは,近赤外線で2フォトンの刺激によってM2受容体を効果的に活性化し,より深い組織への浸透を可能にしました.

結論:

PAIは心臓機能を調節するための非遺伝的,光誘導方法を提供します.
このアプローチは伝統的な光遺伝学の限界を克服し新しい心臓治療法への道を開きます
近赤外線の活性化により心臓内視画像と制御の可能性が広がります

さらに関連する動画

A Cardiac Microphysiological System for Studying Ca2+ Propagation via Non-genetic Optical Stimulation

08:29

A Cardiac Microphysiological System for Studying Ca²⁺ Propagation via Non-genetic Optical Stimulation

Published on: March 21, 2025

1.3K

09:33

Determination of the Photoisomerization Quantum Yield of a Hydrazone Photoswitch

Published on: February 7, 2022

3.9K

関連する概念動画

01:25

Cholinergic Receptors: Muscarinic

5.0K

The pharmacological actions of acetylcholine are elicited via its binding to two families of cholinergic receptors or cholinoceptors, namely, muscarinic and nicotinic receptors. Muscarinic receptors are G protein-coupled receptors and have five subtypes, M1–M5. All mAChR subtypes are activated by acetylcholine and blocked by the antagonist, atropine.
The subtypes M1, M3, and M5 couple with the Gq subunit and activate the phospholipase C (PLC) activity, mobilizing intracellular Ca2+....

5.0K

01:21

Transfer Function in Control Systems

1.5K

The transfer function is a fundamental concept in the analysis and design of linear time-invariant (LTI) systems. It offers a concise way to understand how a system responds to different inputs in the frequency domain. It serves as a bridge between the time-domain differential equations that describe system dynamics and the frequency-domain representation that facilitates easier manipulation and analysis.
To derive the transfer function, consider a general nth-order linear time-invariant...

1.5K

01:20

Antiasthma Drugs: Muscarinic Receptor Antagonists

1.7K

Muscarinic receptor antagonists, also known as antimuscarinic agents, are a class of bronchodilators used to treat asthma, although they are more commonly used to treat COPD. They work by inhibiting the action of acetylcholine (ACh), a neurotransmitter, on muscarinic receptors found in the airways.
Antimuscarinic agents compete with ACh for the same binding site on the muscarinic receptors. By binding to these receptors, they inhibit the downstream effects of ACh and block the parasympathetic...

1.7K

01:24

Glucagon-like Receptor Agonists

877

Incretins include glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which stimulate insulin secretion post-meals. In type 2 diabetes, GIP's efficacy is reduced, making GLP-1 a viable drug target. GIP originates from preproGIP.
GLP-1, when administered in high doses intravenously, triggers insulin secretion, inhibits glucagon release, slows gastric emptying, reduces food intake, and restores normal insulin secretion. However, its rapid inactivation by...

877

01:30

Adrenergic Agonists: Therapeutic Uses

1.8K

Adrenergic agonists have diverse therapeutic uses across various medical conditions and emergencies.
Emergency and Intensive Care Unit (ICU) applications: Pressor agents increase blood pressure, heart rate, and contractility in shock and organ failure situations. Dopamine can induce vasodilation and stimulate adrenoceptors. Endogenous catecholamines are effective in treating cardiogenic shock. α2-agonists like clonidine can reverse anesthesia-induced hypertension.
Allergies and...

1.8K

01:25

Drug-Receptor Interaction: Agonist

4.1K

Agonists are drugs that interact with specific receptors in the body to produce a biological response. When an agonist binds to a receptor, it activates or enhances the receptor's function, leading to physiological effects. The interaction between agonist drugs and receptors is crucial for their therapeutic action in various medical treatments.
Agonists can bind to receptors in different ways. Some agonists bind directly to the receptor's active site, mimicking the endogenous...