ADRA1 - Alpha-1A(1B) (1C) Adrenergic receptor | Elisa - Clia - Antibody - Protein

Background

The adrenergic receptors are a class of G protein-coupled receptors (GPCRs) that respond to the neurotransmitter adrenaline (epinephrine) and noradrenaline (norepinephrine). The alpha-1 adrenergic receptor (ADRA1) is one subtype of adrenergic receptors, and it has three main subtypes: Alpha-1A (ADRA1A), Alpha-1B (ADRA1B), and Alpha-1D (ADRA1D). ADRA1A is primarily located in vascular smooth muscle cells and plays a role in vasoconstriction, leading to an increase in blood pressure. Activation of ADRA1A receptors can also stimulate smooth muscle contraction in other tissues, such as the bladder and uterus. This receptor subtype is also involved in regulating neurotransmitter release in the central nervous system. ADRA1B receptors are primarily found in the heart, vascular smooth muscle, and central nervous system. In the cardiovascular system, ADRA1B activation leads to vasoconstriction and increased heart rate, contributing to the regulation of blood pressure. In the central nervous system, ADRA1B receptors modulate neurotransmitter release and neuronal activity.ADRA1D is primarily expressed in smooth muscle cells of the vasculature, gastrointestinal tract, and urinary bladder. ADRA1D receptors play a role in regulating vascular tone, gastrointestinal motility, and bladder function. Activation of ADRA1D receptors leads to vasoconstriction and smooth muscle contraction.

Protein Structure

The α1-adrenergic receptors share a common structure typical of GPCRs:

• Seven Transmembrane Domains: Characteristic of GPCRs, these domains span the cell membrane.
• Extracellular N-terminus: Important for ligand binding.
• Intracellular C-terminus: Involved in signaling and interaction with G proteins and other intracellular molecules.
• Ligand Binding Site: Located within the transmembrane regions.

Classification and Subtypes

The ADRA1 family consists of three subtypes based on their gene encoding and tissue distribution:

• ADRA1A: Encodes the α1A-adrenergic receptor, primarily found in the prostate, heart, and brain.
• ADRA1B: Encodes the α1B-adrenergic receptor, predominantly expressed in the liver, heart, and cerebral blood vessels.
• ADRA1D: Encodes the α1D-adrenergic receptor, mainly located in the vascular smooth muscle, brain, and spinal cord.

Function and Biological Significance

Alpha-1 adrenergic receptors mediate various physiological responses through their interaction with G proteins, particularly the Gq/11 protein, leading to activation of the phospholipase C (PLC) pathway and subsequent intracellular signaling cascades:

1. Vasoconstriction: Activation of α1-ARs in vascular smooth muscle causes vasoconstriction, increasing blood pressure.
2. Smooth Muscle Contraction: These receptors induce contraction of smooth muscle in the genitourinary system, gastrointestinal tract, and respiratory tract.
3. Cardiac Function: α1-ARs contribute to positive inotropic effects, enhancing the force of heart contractions.
4. Metabolic Regulation: They are involved in glycogenolysis and gluconeogenesis in the liver.

Interactions

1. Gq/11 Protein: Upon activation, α1-ARs interact with Gq/11 proteins, leading to the activation of PLC and production of inositol trisphosphate (IP3) and diacylglycerol (DAG).
2. Phospholipase C (PLC): Activation of PLC results in increased intracellular calcium levels and activation of protein kinase C (PKC).
3. Second Messengers: IP3 and DAG serve as second messengers in the signal transduction pathway, leading to various cellular responses.

Clinical Significance

1. Hypertension: Dysregulation of α1-AR activity is implicated in the pathophysiology of hypertension. Alpha-1 blockers are used as antihypertensive agents.
2. Benign Prostatic Hyperplasia (BPH): α1-AR antagonists, particularly targeting α1A and α1D subtypes, are used to relieve urinary symptoms associated with BPH.
3. Heart Failure: Overactivation of α1-ARs can contribute to cardiac hypertrophy and heart failure. However, their role in heart failure is complex and sometimes beneficial due to positive inotropic effects.
4. Raynaud's Phenomenon: Alpha-1 blockers can be used to treat this condition by reducing vasoconstriction in peripheral blood vessels.

Summary

Alpha-1 adrenergic receptors (α1-ARs), including subtypes α1A, α1B, and α1D, are GPCRs that mediate critical physiological responses through interaction with catecholamines. These receptors are involved in vasoconstriction, smooth muscle contraction, cardiac function, and metabolic regulation. They activate Gq/11 proteins, leading to intracellular signaling via the PLC pathway. Clinically, α1-ARs are significant in conditions such as hypertension, benign prostatic hyperplasia, heart failure, and Raynaud's phenomenon. Understanding the roles and mechanisms of α1-ARs is essential for developing therapeutic strategies targeting these receptors.