By Flavio Guzmán, M.D.
Beta receptors are a subtype of adrenergic receptor (adrenoceptor), their activation triggers a sympathomimetic (adrenergic) response. This article overviews the characteristics related to their physiology and pharmacological aspects. In addition, a related article discusses alpha receptors.
Contents:
– Structure and general characteristics
– Location and physiology of Beta 1 Adrenergic Receptors
– Location and physiology of Beta 2 Adrenergic Receptors
– Beta 3 Adrenergic Receptors
Structure and general characteristics
Beta receptors are G-protein coupled receptors, they act by activating a Gs protein. Gs activates adenylyl cyclase, leading to an increase in levels of intracellular cAMP. Increased cAMP activates protein kinase A, which phosphorylates cellular proteins.
Beta receptors are characterized by a strong response to isoproterenol, with less sensitivity to epinephrine and norepinephrine. The rank order in terms of potency is the following:
isoproterenol > epinephrine > norepinephrine
Beta receptors are subdivided into three subgroups, beta 1, 2, and 3. This division is mainly based on their affinities to adrenergic agonists and antagonists.
Beta 1 receptors
Beta 1 receptors are located mainly at the heart and the kidney, their main effects are depicted below.
Heart
– Increase in chronotropy (heart rate) and inotropy (force of contraction)
Tachycardia results from a Beta 1 mediated increase in the rate of phase 4 depolarization of sinoatrial node pacemaker cells. The inotropic effect is mediated by increased phosphorylation of Ca ++ channels, including calcium channels in the sarcolemma and phospholamban in the sarcoplasmatic reticulum
– Increase in AV- node conduction velocity
Beta 1 stimulated increase in Ca entry increases the rate of despolarization of AV node cells.
Kidney
Beta 1 receptors are present mainly on yuxtaglomerular cells, where receptor activation causes renin release.
Beta 2 receptors
In this section Beta 2 receptors will be studied in two diagrams. The first highlights effects after Beta 2 activation in two systems (respiratory and reproductive), this is viewed separately because of the clinical relevance of Beta 2 agonists in clinical practice. The second figure shows the remaining sympathomimetic effects elicited by Beta 2 receptor activation in other systems.
Bronchial smooth muscle
Beta 2 receptor activation promotes bronchodilation, this physiological property is enhanced by inhaled Beta 2 agonists used in the treatment of asthma and COPD. Some drugs under this category include: salbutamol (albuterol in the US), salmeterol, formoterol and terbutaline.
Uterine contraction
Drugs that bind to Beta 2 receptors (Beta 2 agonists) are used in the treatment of premature labour, this clinical application illustrates how Beta 2 receptors mediate tocolysis on the uterine muscle. Ritodrine is an example of a tocolytic drug.
Bladder detrusor muscle: adrenergic activation of Beta 2 receptors at the bladder promotes relaxation. Bladder constriction is activated by the parasympathetic system, therefore drugs that activate muscarinic receptors such as bethanechol are used in the treatment of urinary retention.
Eye ciliary muscle: this muscle controls eye accomodation and regulates the flow of aqueous humour. Its sympathetic innervation is mediated by Beta 2 receptors.
GI tract: adrenergic activation of the gastrointestinal tract produces a slowing of peristaltic movements (decreased motility) and secretions. These changes are mediated by Beta 2 receptors.
Liver: hyperglycemia and lipolysis occur when Beta 2 receptors are activated. Glucose metabolism is potentiated through gluconeogenesis and glycogenolysis.
Vascular smooth muscle: while Alpha 1 receptors mediate vasoconstriction, Beta 2 receptors induce vasodilation in muscle and liver.
It has been recently proposed that Beta 3 receptors are linked to the regulation of body weight. Located mainly in adipose tissue, Beta 3 receptors promote lipolysis.
References and further reading
Katzung, B. “Basic & Clinical Pharmacology”, 10th Edition. Mc Graw Hill Medical: 2007