Pharmacodynamics

Receptor Down-Regulation

TRReseptör Down-Regülasyonu
Also known as:Downregulation · Receptor downregulation

A decrease in the number of receptors available at the cell surface or in the cell, typically in response to prolonged or excessive agonist stimulation, which reduces tissue responsiveness.

In depth

After agonist binding, many GPCRs are phosphorylated by G protein-coupled receptor kinases (GRKs) and bound by β-arrestins, which uncouples them from G proteins (desensitisation) and targets them for endocytosis. Internalised receptors are recycled or degraded in lysosomes; with sustained exposure, increased degradation and reduced synthesis lower total receptor number, a slower process than acute desensitisation that develops over hours to days.

Down-regulation is a major mechanism of pharmacodynamic tolerance (e.g. to β2-agonists) and underlies the therapeutic use of continuous GnRH agonists, which suppress gonadotropin release by desensitising and down-regulating pituitary GnRH receptors.

Clinical pearl

Continuous GnRH agonist therapy causes an initial surge in LH and testosterone before suppression, which is why an antiandrogen is commonly given at the start of treatment for prostate cancer.

Example drugs

Salbutamol leuprorelin Goserelin
TRIn Turkish

Reseptör Down-Regülasyonu

Genellikle bir agonistle uzun süreli veya aşırı uyarıma yanıt olarak hücre yüzeyinde ya da hücrede bulunan reseptör sayısının azalması ve buna bağlı olarak dokunun yanıt verme yeteneğinin düşmesidir.

Agonist bağlandıktan sonra birçok GPCR, G proteinine kenetli reseptör kinazları (GRK) tarafından fosforile edilir ve β-arrestinlere bağlanır; bu durum reseptörü G proteininden ayırır (desensitizasyon) ve endositoza yönlendirir. İçeri alınan reseptörler ya membrana geri döner ya da lizozomlarda yıkılır; maruziyet sürdüğünde artan yıkım ve azalan sentez toplam reseptör sayısını düşürür. Bu süreç akut desensitizasyondan daha yavaştır ve saatler ile günler içinde gelişir.

Down-regülasyon farmakodinamik toleransın başlıca mekanizmalarından biridir (örneğin β2-agonistlere karşı) ve sürekli GnRH agonisti uygulamasının tedavi edici etkisinin temelini oluşturur: hipofizdeki GnRH reseptörlerinin desensitizasyonu ve down-regülasyonu gonadotropin salınımını baskılar.

Sürekli GnRH agonisti tedavisi, baskılanmadan önce LH ve testosteron düzeylerinde başlangıçta bir artışa (flare) yol açar; bu nedenle prostat kanseri tedavisinin başında genellikle bir antiandrojen eklenir.

Diğer adları:Aşağı regülasyon · Down-regülasyon · Reseptör sayısında azalma
Updated 24.09.2026 0 views Educational reference — verify against current sources before clinical use.

Read next

Receptor Up-RegulationReseptör Up-Regülasyonu

An increase in the number or sensitivity of receptors, typically after prolonged receptor blockade or reduced exposure to the endogenous agonist (e.g. denervation), leading to tissue supersensitivity.

 ToleranceTolerans

A gradual reduction in response to a drug with repeated or continuous exposure, so that a higher dose is needed to reproduce the original effect; it develops over days to weeks.

 TachyphylaxisTaşifilaksi

A rapidly developing decrease in response to a drug after repeated doses over a short period (minutes to hours), which often cannot be overcome by increasing the dose.

 G Protein-Coupled ReceptorG Proteinine Kenetli Reseptör

A member of the largest family of cell-surface receptors, a single polypeptide with seven transmembrane α-helices that transduces ligand binding into intracellular signals by activating heterotrimeric G proteins.

 AgonistAgonist

A drug or endogenous substance that binds to a receptor and activates it, producing a biological response; it possesses both affinity and efficacy (intrinsic activity).

 ReceptorReseptör

A macromolecule, usually a protein, to which a drug or endogenous ligand binds specifically and thereby initiates a change in cell function that produces a biological response.