Genetika, stavba, přenos signálu adrenergních receptorů beta 3
Adrenoceptors - adrenergic receptors
- Rhodopsin-like G protein-coupled receptors
- Targets of the catecholamines
- Especially norepinephrine (noradrenaline) and epinephrine (adrenaline)
- Many cells possess these receptors, and the binding of a catecholamine to the receptor will generally stimulate the sympathetic nervous system
- 3 classes of adrenoceptors
- Alpha 1 (a Gq coupled receptor)
- Alpha 2 (a Gi coupled receptor)
- Beta (a Gs coupled receptor)
- Each can be further divided into subtypes [PMID: 2855960]
- Different subtypes can coexist in some tissues, but one subtype normally predominates.
3 subtypes of beta adrenoceptors (beta 1-3)
- Based on their affinities to adrenergic agonists and antagonists
- All three subtypes act in the main by activating a Gs protein [PMID: 11053129]
- Activating adenylate cyclase activity
- Beta 2 subtype also couples to Gi/o protein [PMID: 11053129, PMID: 12063255]
- Beta adrenoceptor selective agonists (beta blockers)
- Treatment of asthma, angina, cardiac conditions, migraine, anxiety disorders, hyperthyroidism, topically in glaucoma [PMID: 15655528] [10]
Stavba
- Shares the structure of typical GPCRs
- 40–50% amino acid sequence similarity with B1- and 2-AR
- Key differences
- Third intracytoplasmic loop
- C-terminal tail
- B3AR lacks the consensus sequences for phosphorylation by
- PKA
- BARK
- Or GRK2 in the cardiac myocytes
- Known to mediate the beta -arrestin recruitment
- Internalization of the receptor which
- Homologous desensitization [12]
- B3AR is less prone (than B1- or B2-ARs) to the progressive loss of coupling and efficacy in response to prolonged stimulation by catecholamines
- Verified in the specific context of cardiac myocytes [12]
Transdukce signálu B3AR
Gs protein coupled with beta 3-AR
- Lead to increased activity of the enzyme adenylyl cyclase leads to
- Increased formation of cyclic adenosine monophosphate (cAMP) [1 ]
Gi proteins couple with beta 3-AR
- Lead to decrease in intracellular cAMP [1]
- Proposed as a mechanism of action in the heart
- Can act as a brake on beta 1- and beta 2 adrenergic receptors
- To prevent over-activation
- By opposing the classical inotropic effect of beta 1 and beta 2 adrenergic receptors [1]
