### Date : 2024-10-31 13:29
### Topic : Adrenergic receptors
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Adrenergic receptors are a group of G-protein-coupled receptors (GPCRs) that are targets for the catecholamines *epinephrine (adrenaline)* and *norepinephrine (noradrenaline)*. They play a crucial role in the sympathetic nervous system, mediating various physiological responses like heart rate, vascular tone, and metabolic regulation. These receptors are broadly classified into **alpha (α)** and **beta (β)** receptors, each with further subtypes.
### 1. **Alpha (α) Receptors**
Alpha receptors are primarily involved in *vasoconstriction* and *smooth muscle contraction*. They are further divided into α1 and α2 receptors.
- **α1 Receptors**
- **Location**: Blood vessels (arterioles and veins), bladder sphincter, radial muscle of the iris, and prostate.
- **Function**: Causes smooth muscle *contraction* leading to:
- *Vasoconstriction*: Increases peripheral resistance and raises blood pressure.
- *Mydriasis*: Pupil dilation due to contraction of the radial muscle of the iris.
- *Urinary retention*: Contraction of the bladder sphincter.
- **Mechanism**: Works through the *Gq protein* pathway, which activates phospholipase C (PLC), leading to an increase in intracellular calcium and smooth muscle contraction.
- **α2 Receptors**
- **Location**: Presynaptic nerve terminals, pancreas, and some blood vessels.
- **Function**: Inhibits norepinephrine release, causing:
- *Decreased sympathetic outflow*: This reduces blood pressure.
- *Inhibition of insulin release*: Reduces insulin secretion from pancreatic β-cells.
- **Mechanism**: Works through the *Gi protein* pathway, inhibiting adenylate cyclase, reducing cyclic AMP (cAMP), leading to a decreased release of norepinephrine.
### 2. **Beta (β) Receptors**
Beta receptors are mainly involved in *smooth muscle relaxation*, *cardiac stimulation*, and *metabolic effects*. They are divided into β1, β2, and β3 receptors.
- **β1 Receptors**
- **Location**: Heart (myocardium, SA node), kidneys.
- **Function**: Enhances cardiac function by:
- *Increased heart rate* (positive chronotropy).
- *Increased force of contraction* (positive inotropy).
- *Increased renin release* from the kidneys, leading to the activation of the renin-angiotensin-aldosterone system (RAAS), which increases blood pressure.
- **Mechanism**: Works through the *Gs protein* pathway, which stimulates adenylate cyclase, increasing cAMP levels and enhancing cardiac contractility.
- **β2 Receptors**
- **Location**: Smooth muscle of the lungs (bronchi), blood vessels (skeletal muscle), uterus, liver.
- **Function**: Causes smooth muscle *relaxation* leading to:
- *Bronchodilation*: Useful for asthma management.
- *Vasodilation*: Decreases peripheral resistance, especially in skeletal muscles.
- *Relaxation of uterine smooth muscle*: Prevents preterm labor.
- *Glycogenolysis and gluconeogenesis*: Increases blood glucose levels.
- **Mechanism**: Works through the *Gs protein* pathway, increasing cAMP levels, leading to smooth muscle relaxation.
- **β3 Receptors**
- **Location**: Adipose tissue, bladder.
- **Function**: Involved in:
- *Lipolysis*: Breakdown of fat in adipose tissue.
- *Bladder relaxation*: Reduces bladder overactivity.
- **Mechanism**: Also works through the *Gs protein* pathway, increasing cAMP, which stimulates lipolysis in adipocytes.
### Summary Table
| Receptor | Location | Function | Pathway |
|----------|----------|----------|---------|
| **α1** | Blood vessels, bladder | Vasoconstriction, pupil dilation | Gq (↑Ca²⁺) |
| **α2** | Presynaptic terminals, pancreas | ↓ Norepinephrine release, ↓ insulin | Gi (↓cAMP) |
| **β1** | Heart, kidneys | ↑ Heart rate, ↑ renin release | Gs (↑cAMP) |
| **β2** | Lungs, skeletal muscle vessels, uterus | Bronchodilation, vasodilation | Gs (↑cAMP) |
| **β3** | Adipose tissue, bladder | Lipolysis, bladder relaxation | Gs (↑cAMP) |
### Clinical Relevance
- **Agonists** of α1 receptors are used to treat hypotension (e.g., *phenylephrine*).
- **α1 Blockers** like *prazosin* are used for hypertension and benign prostatic hyperplasia (BPH).
- **β1 Agonists** (e.g., *dobutamine*) are used in heart failure to increase cardiac output.
- **β1 Blockers** (e.g., *metoprolol*) are used to manage hypertension and heart failure by reducing cardiac workload.
- **β2 Agonists** (e.g., *albuterol*) are used for asthma as they promote bronchodilation.
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