Gタンパク質の活性化により,カルシウムチャネルリガンドに対するアゴニスト反応が促進されます
1Department of Pharmacology, St George's Hospital Medical School, London, UK.
Nature
|December 24, 1987
まとめ
グアニンヌクレオチド結合 (G) タンパク質は,カルシウムチャネル活動を調節する. 活性化されたGタンパク質は,カルシウムチャネル電流を強化し,リガンド相互作用を強化し,細胞応答に影響を与えます.
科学分野:
- 神経科学は神経科学である.
- 分子生物学は分子生物学である.
- 薬理学 薬理学とは
背景:
- グアニンヌクレオチド結合 (G) タンパク質の活性化は,電圧活性化カルシウムチャネルの受容体媒介抑制に不可欠です.
- GTP アナログは,受容体アゴニストを強化し,背根ギャングリオン (DRG) ニューロンにおけるカルシウム電流を阻害する.
- 持続的なL型カルシウムチャネル電流成分は,グアノシン5'-O-3-チオトリホスファート (GTP-ガンマ-S) による抑制に抵抗性があります.
研究 の 目的:
- カルシウムチャネルアンタゴニストとGTP-ガンマ-S改変電流の相互作用を調査する.
- カルシウムチャネルリガンドの相互作用に対する活性化Gタンパク質の影響を調査する.
- カルシウムチャネルリガンドに対する細胞応答に対するグアニンヌクレオチド効果の電気生理学的証拠を提供するため.
主な方法:
- 培養DRGニューロンにおけるカルシウムチャネル電流の電気生理学的記録.
- GTP アナログおよびカルシウムチャネルアンタゴニスト (D600,ニフェディピン,ディルチアゼム) の使用.
- GTP-ガンマ-S-改変電流に対する pertussis toxinの効果の評価.
主要な成果:
- カルシウムチャネル抗生物質は,内部GTP-gamma-S.S.の存在下で,カルシウムチャネル電流を著しく強化した.
- この増強は pertussis toxinによって廃止され,Gタンパク質の関与 (Gi/Go) を示した.
- 活性化されたGタンパク質は,カルシウムチャネルと相互作用し,リガンドの作用を強める.
結論:
- 活性化されたGタンパク質は,カルシウムチャネルと相互作用し,チャネルリガンドの効果を強める.
- この相互作用は,静止状態のチャネルにおけるアゴニスト部位でのリンガンド結合を強化する.
- ガニンヌクレオチドがカルシウムチャネルリガンドに対する細胞反応に影響を与えるという最初の電気生理学的証拠を示しています.
さらに関連する動画
関連する概念動画
G Protein-coupled Receptors
G Protein-Coupled Receptors or GPCRs are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to sensory stimuli such as light, odors, hormones, cytokines, or neurotransmitters.
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...
Activation and Inactivation of G Proteins
Heterotrimeric G proteins are guanine nucleotide-binding proteins. As the name suggests, heterotrimeric G proteins are composed of three subunits: alpha, beta, and gamma. They remain GDP-bound or GTP-bound inside the cells and switch between inactive/active states. The Gα subunit possesses the nucleotide-binding pocket that binds guanine nucleotides and switches between GDP or GTP-bound states. In contrast, the Gꞵ and Gγ subunits are always bound together with high affinity and are together...
G-Protein Gated Ion Channels
GPCRs are primarily responsible for our sense of smell, taste, and vision. The binding of a sensory stimulus activates GPCR to stimulate effector proteins, many of which are ion channels in the sensory organs. GPCRs modulate the opening and closing of the target ion channels either directly by binding them, or by releasing second messengers that activate these channels. As ions move across the membrane, the membrane potential is altered, which induces an appropriate response.
Sensory organs,...
Sensory organs,...
GPCRs Regulate Adenylyl Cylase Activity
Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of cells.
Two...
Two...
Calmodulin-dependent Signaling
Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
Ligand-Gated Ion Channel Receptor: Gating Mechanism
Ligand-gated ion channels are transmembrane proteins that play a vital role in intercellular communication and functions of the nervous system. They allow the influx of ions across the membrane once the neurotransmitter binds, allowing the subsequent transmission of electrical excitation across the neurons. Other ligand-gated ion channels, like the γ-aminobutyric acid (GABA) receptor, permit anions like chloride into the cells on the binding of the GABA molecule. Their entry into the cell...


