Beta-1 adrenergic receptor

  • OMIM: 109630
  • UniProt: P08588
  • MGI: 87937

The β1 -adrenoceptor, often called β1 -adrenergic receptor, a cell membrane - bound protein belonging to the family of G- protein-coupled receptors, beta- adrenergic receptors. It is activated by the hormone epinephrine and is responsible among other things for the effect on the heart. The β1 - adrenoceptor is the molecular target of one of the most important groups of drugs, the beta-blockers.

Occurrence

The β1 - adrenoceptor shows a wide distribution within the subphylum of vertebrates. He could be detected both in fish, amphibians, reptiles, birds and mammals. The evolutionary origin of the β1 - adrenoceptor and the spin-off to other β - adrenergic receptors by gene duplication can be extrapolated to the late Neoproterozoic or early Paleozoic.

In the human organism the β1 - adrenoceptor is especially found in the heart. In the heart it is with a share of 70 to 80 % of the dominant β - adrenoceptor.

The β1 - adrenoceptor is also found on cells in the kidney, the juxtaglomerular cells. About a stimulation occurs on renin secretion.

Biochemistry

Genetics

The β1 - adrenoceptor is encoded by the intron-free ADRB1 gene. ADRB1 the gene of the human is located on chromosome 10 at 10q24 - q26 locus. Polymorphisms of the gene are associated among other things with heart failure and a change in the effectiveness of beta-blockers.

Structure

The β1 - adrenoceptor was one of the first G- protein -coupled receptors, whose structure was elucidated by means of X-ray crystallography. As a characteristic motif of the β1 - adrenoceptor, like all other known G protein-coupled receptors that span the cell membrane seven α - helices. As with rhodopsin itself an eighth α -helix connects to the intracellular end of transmembrane helix 7. In addition, the β1 - adrenoceptor features similar to the β2 - adrenoceptor, via another α -helical structural motif, which is located extracellularly between the Tansmembranhelices 4 and 5. A ligand binding site, to which the endogenous ligand adrenaline and numerous drugs bind, is located on the outer side of the cell transmembrane helices. The cell- inner loops in contrast carry binding sites for the effector proteins involved in signal transduction, in particular G- proteins.

Receptor activation

The β1 - adrenoceptor is activated by binding of its endogenous ligands epinephrine and norepinephrine. By the binding of an agonistic ligand, the ligand-binding site is contracted and stabilizes the active state of the receptor. In this state, the receptor is able to activate G proteins intracellularly bound and thus to start a signal transduction cascade. About the β1 - adrenoceptor Gs proteins are preferentially activated, which in turn activate adenylyl cyclases and increase intracellular cAMP levels.

Function

The β1 - adrenoceptor is the most significant adrenoceptor on heart. He is primarily responsible for increasing contractility (positive inotropy ), heart rate increasing (positive chronotropy ), conduction accelerating (positive Dromotropie ) and threshold -lowering effect (positive Bathmotropie ) of adrenaline to the heart.

Pharmacology

The β1 - adrenoceptor is one of the pharmacologically significant targets for drug development. Antagonists of the β1 - adrenergic receptor, the so-called beta blockers, which include the drugs atenolol, bisoprolol, carvedilol, metoprolol, nebivolol, propranolol, sotalol and timolol include, in particular in the treatment of hypertension, coronary heart disease, heart failure, heart rhythm disturbances and migraine used.

β1 - adrenoceptor agonists, such as epinephrine, norepinephrine and dobutamine are used in anesthesia and intensive and emergency medicine.

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