Pharmacodynamics

Second Messenger

TRİkinci Haberci
Also known as:Intracellular messenger

A small intracellular signalling molecule or ion, such as cAMP, cGMP, IP3, diacylglycerol or Ca²⁺, whose concentration changes in response to receptor activation and which relays and amplifies the signal inside the cell.

In depth

The first messenger (hormone, neurotransmitter or drug) acts on a receptor, and second messengers are generated by effector enzymes: adenylyl cyclase produces cAMP (activating protein kinase A), guanylyl cyclase produces cGMP (protein kinase G), and phospholipase C cleaves PIP2 into IP3, which releases Ca²⁺ from the endoplasmic reticulum, and diacylglycerol (DAG), which activates protein kinase C. Each step amplifies the signal.

Signals are terminated by degradation or sequestration, e.g. hydrolysis of cAMP and cGMP by phosphodiesterases (PDEs). Drugs can therefore act by modulating second-messenger levels: PDE5 inhibitors raise cGMP, nitrates stimulate soluble guanylyl cyclase via nitric oxide, and milrinone raises cardiac cAMP by inhibiting PDE3.

Clinical pearl

Nitrates and PDE5 inhibitors both raise cGMP and together can cause profound hypotension, so their combination is contraindicated.

Example drugs

Sildenafil glyceryl trinitrate Milrinone Theophylline
TRIn Turkish

İkinci Haberci

Reseptör aktivasyonuna yanıt olarak hücre içi konsantrasyonu değişen ve sinyali hücre içinde ileterek güçlendiren cAMP, cGMP, IP3, diaçilgliserol veya Ca²⁺ gibi küçük bir sinyal molekülü ya da iyondur.

İlk haberci (hormon, nörotransmiter veya ilaç) reseptöre etki eder; ikinci haberciler ise efektör enzimler tarafından oluşturulur: adenilil siklaz cAMP'yi (protein kinaz A'yı aktive eder), guanilil siklaz cGMP'yi (protein kinaz G'yi aktive eder) üretir; fosfolipaz C ise PIP2'yi, endoplazmik retikulumdan Ca²⁺ salıveren IP3'e ve protein kinaz C'yi aktive eden diaçilgliserole (DAG) ayırır. Her basamak sinyali amplifiye eder.

Sinyaller yıkım ya da hücre içi depolara geri alınma (sekestrasyon) ile sonlandırılır; örneğin cAMP ve cGMP fosfodiesterazlar (PDE) tarafından hidroliz edilir. Bu nedenle ilaçlar ikinci haberci düzeylerini değiştirerek etki gösterebilir: PDE5 inhibitörleri cGMP'yi artırır, nitratlar nitrik oksit aracılığıyla çözünür guanilil siklazı uyarır, milrinon ise PDE3'ü inhibe ederek kalpte cAMP'yi artırır.

Nitratlar ve PDE5 inhibitörleri cGMP düzeyini artırır; birlikte kullanıldıklarında ağır hipotansiyona yol açabildiklerinden bu kombinasyon kontrendikedir.

Diğer adları:İkincil haberci · İkinci ulak · Hücre içi haberci
Updated 24.09.2026 1 views Educational reference — verify against current sources before clinical use.

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