Receptors and what do they do Flashcards
What are some of the major branches of Receptors and how are they categorized?
G Protein-Coupled Receptors (GPCRs), Ion Channel Receptors, Receptor Tyrosine Kinases (RTKs), Intracellular Receptors, and Toll-like Receptors (TLRs).
They can be broadly categorized based on their structure, mechanism of action, and the type of ligands they bind.
GPCR’s; what are some features
Only found in Eukaryotes due to the complexity of their cellular organization, the need for sophisticated intercellular communication in multicellular organisms, and the evolutionary pathways that led to their development. Eukaryotic cells benefit from the versatility and precision of GPCR-mediated signaling, which allows them to manage a wide range of physiological processes and adapt to changing environments more effectively than the simpler signaling mechanisms found in prokaryotes.
Ligands that bind to these receptors range from: light sensitive compounds, odors, phermones, hormones and neurotransmitters to name a few
GDP - is bind by the alpha subunit when inactive
GTP - is bind by the alpha subunit when active
per Khan academeny here is the link: https://www.khanacademy.org/science/ap-biology/cell-communication-and-cell-cycle/changes-in-signal-transduction-pathways/v/g-protein-coupled-receptors
Common Features:
Structure: Seven transmembrane alpha-helices.
Mechanism: Activate G proteins (Gq, Gi, Gs) which then modulate various intracellular signaling pathways (e.g., adenylate cyclase, phospholipase C).
Location: Cell membrane.
Function: Diverse physiological roles including neurotransmission, immune responses, and hormonal regulation.
Response Time: Seconds to minutes.
(think of the second messenger as to why this is true of the time it takes)
Examples: Adrenergic receptors (α1, α2, β1, β2), muscarinic acetylcholine receptors (M1-M5), dopamine receptors (D1-D5)
Ion Channel Receptors; what are some features
Common Features:
Structure: Transmembrane proteins forming a pore.
Mechanism: Ligand binding causes conformational change, opening the channel and allowing ion flow (Na+, K+, Ca2+, Cl-).
Location: Cell membrane.
Function: Fast synaptic transmission, muscle contraction, and sensory perception.
Ligands: Neurotransmitters (e.g., acetylcholine for nicotinic receptors, GABA for GABA receptors).
Response Time: Milliseconds.
Examples: Nicotinic acetylcholine receptors, GABAA receptors, NMDA receptors.
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The above describes LIgand-gated ion channels there are 2 others channels that are similar but not the same:
- Voltage gated channel- works by a difference in membrane potention. The action potential
https://www.youtube.com/watch?v=KTTeD2AMiPA - Stretch activated/ mechanical- deformation of the cell membrane
Enzyme linked receptors, the most common are called Receptor Tyrosine Kinases (RTKs); What are some features
Common Features:
Structure: Single transmembrane helix, extracellular ligand-binding domain, intracellular kinase domain.
Mechanism: Ligand binding induces dimerization and autophosphorylation, activating downstream signaling pathways (e.g., MAPK/ERK, PI3K/Akt). RTKS often occurs in pairs because 1 RTK will phosphorylate the other one reinforcing what is stated above
Location: Cell membrane.
Function: Cell growth, differentiation, metabolism, and survival.
Differences:
Ligands: Growth factors (e.g., EGF, VEGF), hormones (e.g., insulin).
Response Time: Minutes to hours.
Examples: Epidermal growth factor receptor (EGFR), insulin receptor, vascular endothelial growth factor receptor (VEGFR)
pic by: https://www.youtube.com/watch?v=5LQ1iL43bmQ
What are cholinergic receptors?
Parasympathetic Nervous System (PANS)
Sympathetic Nervous System (SANS)
They are a type of ligand gated ion receptors (Nicotinic) and G-protein Coupled receptor (Muscarinic) that bind Acetylcholine (ACh). Nicotinic and Muscarinic receptors are the 2 types of cholinergic receptors
There are 2 types of Nicotinic receptors
Nm - located on skeletal muscles
Nn - located on neurons and adrenal medulla (modified ganglion no post ganglionic fibers so it just secrestes epinephrine and norepinephrine directly into the )
Muscarinic
M1, M3, M5: Gq –> Ca –> Contraction of smooth muscle and gland
M2, M4: Gi –> inhibition of parasympathetic functions
All of the muscarinic receptors are GPCR’s
Location it can be found
Nm - Skeletal muscle; in particular the sarcolemma within the neuromuscular junction. Depolarizes the membrane which results in muscular contraction
Nn- All peripheral ANS ganglia
Found on Dendrites of the post-ganglionic sympathetic and parasympathetic neurons including chromaffin cells on the adrenal medula
Muscarinic receptors
smoooth mucles, and cardiac muscles
Peripheral tissues
- Heart
- Eyes
- GI Tract
M1, M3 Glands
M3: eye
M2: Heart - due to PANS wants to inhibit heart; negative chronotropy, ionotropy, dromotropy
M3: Lungs
M3: GI/GU
M3: Blood vessels dilate via NO: to cause sweating (SANS), tears, salivation, bronchial secretions etc. of the glands
Hint To remember:
B1, B2 - heart, lungs
M1, M2, M3- Brain, Heart, lungs/tongue (glands)
These are numbered based off of its importance and the brain is more important than the heart and so on.
https://www.youtube.com/watch?v=lSd2s3on5HA
What type of receptor is Muscarinic receptor and what does it effect?
G-proteing Coupled Receptor
Muscarinic receptors
Mainly peripheral tissues. Smoooth mucles, and cardiac ❤️ muscles. M1 in particular has effects on the brain 🧠
M1, M3 Glands
M3: eye
M2: Heart - due to PANS wants to inhibit heart; negative chronotropy, ionotropy, dromotropy
M3: Lungs
M3: GI/GU
M3: Blood vessels dilate via NO: to cause sweating (SANS), tears, salivation, bronchial secretions etc. of the glands
Hint To remember:
B1, B2 - heart, lungs
M1, M2, M3- Brain, Heart, lungs/tongue (glands), etc
These are numbered based off of its importance and the brain is more important than the heart and so on.
What type of receptor is a Nicotinic Receptor and what does it effect?
Ligand gated ion channels.
Skeletal muscles 💪🏾 (Nm) and neurons and adrenal medulla (Nn) (modified ganglion no post ganglionic fibers so it just secrestes epinephrine and norepinephrine directly into the )
There are 2 types of Nicotinic receptors
Nm - located on skeletal muscles at the neuromuscular junction
Nn - located on neurons and adrenal medulla (modified ganglion no post ganglionic fibers so it just secrestes epinephrine and norepinephrine directly into the bloodstream). CNS ganglia, PNS ganglia, and adrenal medulla
Small doeses of Acetylcholine, Nicotine, or Succinylcholine Stimulates. Remember the S’s
High doses of Acetylcholine, Nicotine, or Succinylcholine Hinders its effect as it causes desensitazation.
What type of receptor is an alpha receptor, what are the different types and what does it effect?
A subset of GPCR’s
alpha 1 - Stimulate smooth muscles, glands and organs relevant to the sympathetic nervous system that is not the heart or juxtaglomerular cells or muscles. Hence constricting
Pro-Sympathetic
Gq - associated and if you want to be Gq you need Calcium
alpha 2 - Pre-synaptic terminal of the sympathetic neurons. To modulate NE release
Anti-sympathetic, decreases NE release and thus decreasing the sympathetic functions
sometimes refered to as autoreceptors because they respond to the neurotransmitter released by the same neuron.
Gi - association coupled receptors inhibit Adenylate Cyclase, by decreasing cAMP levels and modulating downstream signaling pathways.
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More indepth:
alpha 1 receptors have 3 subtypes
α1a - Alpha-1A:
Location: Primarily found in the prostate and urethra.
Function: Involved in smooth muscle contraction in the prostate and urinary tract.
α-1B: Blood vessels, targeted for hypertension.
Location: Mainly found in vascular smooth muscle (blood vessels).
Function: Responsible for vasoconstriction, thus regulating blood pressure.
α-1D: Dextrusor muscle and spinal cord, additional effects on urinary function
Location: Present in the detrusor muscle of the bladder, certain vascular tissues, and the central nervous system.
Function: Plays a role in urinary function and potentially in blood vessel tone regulation.
Vascular Smooth Muscle:
Arterioles: Alpha-1 receptors on arteriolar smooth muscle cells mediate vasoconstriction, leading to increased peripheral vascular resistance and blood pressure regulation.
Veins: Alpha-1 receptors on venous smooth muscle cells contribute to venoconstriction, aiding in venous return to the heart.
Urinary System:
Bladder Sphincter Muscle:
Alpha-1 receptors in the urinary bladder sphincter promote contraction, leading to urinary retention and inhibition of urine flow.
Eye (Ocular Muscles):
Iris Dilator Muscle: Alpha-1 receptors in the iris dilator muscle cause pupil dilation (mydriasis), allowing more light to enter the eye.
Male Reproductive System:
Seminal Vesicles: Alpha-1 receptors in seminal vesicles contribute to smooth muscle contraction, aiding in ejaculation and sperm transport.
Vas Deferens: Alpha-1 receptors in the vas deferens also participate in smooth muscle contraction, facilitating sperm movement during ejaculation.
Gastrointestinal Tract:
Some smooth muscle cells in the gastrointestinal (GI) tract express alpha-1 receptors, contributing to GI motility and contraction.
Liver:
Alpha-1 receptors on hepatic vascular smooth muscle cells may influence hepatic blood flow and vascular tone.
Lungs (Bronchioles):
While alpha-1 receptors are not prominent in bronchial smooth muscle (where beta-2 receptors predominate for bronchodilation), they may have some modulatory effects on bronchial tone.
Skin and Subcutaneous Tissues:
Blood vessels in the skin and subcutaneous tissues contain alpha-1 receptors, contributing to local vascular responses and temperature regulation.
What type of receptor is an beta receptor, how many are there and what does it effect?
A subset of GCPR’s
Beta 1 - Stimulates Heart, Juxtaglomerular cells (kidneys)
Beta 2 - All smooth muscles, glands, and organs related to the sympathetic nervous system
Beta 3 - Metabolism of adipose tissue for energy via lipolysis
Are Gs - associated with cAMP
Post ganglionic Beta are Inhibitory on everything except:
1. Heart B1
2. Hormone
3. Metabolism B3
Sympathetic response where does it start, what regions of the CNS are involved, what part of the vetebrae is involved.
It starts from the lateral horn cell and leaves through the ventral horn
Sympathetic response - acts on the thoracolumbar regions and it is involved in fight or flight
What type of fibers are involved in the sympathetic response and how to differentiate between them?
Adrenergic fibers - are post ganglionic fibers
Cholinergic fibers - are pre ganglionic fibers
Preganglionic: Nerve fibers that extend from the CNS to the autonomic ganglia, releasing neurotransmitters (e.g., ACh) at synapses with postganglionic neurons.
Postganglionic: Nerve fibers that extend from the autonomic ganglia to target tissues, releasing neurotransmitters (e.g., ACh or norepinephrine) at their target organs to elicit physiological responses.
How do GPCR’s function
Gq-coupled receptors activate PLC-β, leading to increased intracellular Ca2+ levels and PKC activation.
Gs-coupled receptors stimulate AC, increasing cAMP levels and activating PKA.
Gi-coupled receptors inhibit AC, decreasing cAMP levels and modulating downstream signaling pathways.
Gq-coupled receptors are associated with calcium signaling and cell proliferation, while Gs-coupled receptors are involved in cAMP-mediated processes such as heart rate regulation, smooth muscle relaxation, and metabolic responses. Gi-coupled receptors play a role in inhibiting cAMP-dependent pathways and modulating neurotransmitter release.
Here’s how Gi can inhibit Gq-mediated signaling:
Inhibition of Adenylyl Cyclase (AC):
Gi proteins inhibit adenylyl cyclase (AC), an enzyme responsible for converting ATP into cyclic AMP (cAMP).
Gq-coupled receptors typically activate PLC, leading to the production of inositol trisphosphate (IP3) and diacylglycerol (DAG). IP3 triggers the release of calcium ions (Ca2+) from intracellular stores, while DAG activates protein kinase C (PKC).
However, when Gi proteins are activated, they reduce the activity of AC, resulting in decreased levels of cAMP.
Lower levels of cAMP can lead to decreased activation of protein kinase A (PKA), which is downstream of cAMP signaling pathways.
Cross-Inhibition of Pathways:
The inhibition of AC by Gi proteins can lead to cross-inhibition of pathways activated by Gq proteins.
Specifically, decreased cAMP levels can modulate calcium signaling pathways downstream of Gq-coupled receptors.
Additionally, the reduction in cAMP-dependent protein kinase activity can influence cellular responses mediated by Gq pathways, such as cell proliferation and gene expression.
Modulation of Neurotransmitter Release:
Gi-coupled receptors are also involved in modulating neurotransmitter release in neurons.
By inhibiting AC and reducing cAMP levels, Gi signaling can modulate the release of neurotransmitters, influencing synaptic transmission and neuronal activity
Where are serotonin receptors located,
What type of a receptor is the Dopamine, How many types are there, where is it located
- GPCR
- There are five main types of dopamine receptors, classified into two families: D1-like receptors (D1 and D5) and D2-like receptors (D2, D3, and D4).
- Mesocorticolimbic system (is the short answer)
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Here is more in-depth
D1-Like Receptors:
D1 Receptors:
Location: Predominantly found in the striatum, nucleus accumbens, olfactory tubercle, and frontal cortex.
Function:
Striatum and Nucleus Accumbens: Involved in motor control and reward processing.
Frontal Cortex: Plays a role in cognitive functions and executive decision-making.
Mechanism: Activates adenylyl cyclase via Gs proteins, increasing cyclic AMP (cAMP) levels.
D5 Receptors:
Location: Found in the hippocampus, hypothalamus, and olfactory tubercle.
Function:
Hippocampus: Involved in memory and learning.
Hypothalamus: Regulates hormonal processes and homeostasis.
Mechanism: Similar to D1, activates adenylyl cyclase and increases cAMP levels.
D2-Like Receptors:
D2 Receptors:
Location: Found in the striatum, substantia nigra, pituitary gland, and prefrontal cortex.
Function:
Striatum and Substantia Nigra: Crucial for motor control; dysfunction linked to Parkinson’s disease.
Pituitary Gland: Regulates hormone secretion.
Prefrontal Cortex: Modulates cognitive functions and decision-making.
Mechanism: Inhibits adenylyl cyclase via Gi proteins, decreasing cAMP levels. Also involved in feedback inhibition of dopamine release.
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Modulation of Dopamine Release:
Autoreceptors: D2 receptors can function as autoreceptors on presynaptic dopamine neurons. When dopamine binds to these autoreceptors, it inhibits further release of dopamine, providing a feedback mechanism to regulate dopamine levels in the synapse. This helps prevent overstimulation and maintains a balance in the reward circuitry.
Postsynaptic Inhibition: Postsynaptic D2 receptors in the reward pathways modulate neuronal activity in a way that promotes the perception of reward and pleasure. Inhibiting excessive neuronal firing can fine-tune the response to rewarding stimuli, ensuring that the reward signal is properly processed.
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D3 Receptors:
Location: Concentrated in the limbic areas such as the nucleus accumbens, hypothalamus, and olfactory tubercle.
Function:
Nucleus Accumbens: Implicated in the regulation of mood and reward.
Hypothalamus: Influences hormonal control and emotional responses.
Mechanism: Inhibits adenylyl cyclase, reducing cAMP levels, similar to D2 receptors.
D4 Receptors:
Location: Found in the frontal cortex, amygdala, hippocampus, and hypothalamus.
Function:
Frontal Cortex: Involved in cognitive processes and attention.
Amygdala and Hippocampus: Plays a role in emotional regulation and memory.
Mechanism: Inhibits adenylyl cyclase, reducing cAMP levels.
Functions and Mechanisms:
D1 and D5 Receptors:
Function: Generally stimulate neurons by increasing cAMP levels, which enhances excitatory neurotransmission.
Mechanism: Activation of adenylyl cyclase through Gs proteins, leading to increased cAMP.
D2, D3, and D4 Receptors:
Function: Generally inhibit neurons by decreasing cAMP levels, which reduces excitatory neurotransmission.
Mechanism: Inhibition of adenylyl cyclase through Gi proteins, leading to decreased cAMP.
Summary of Dopamine Receptor Functions:
Motor Control: D1 and D2 receptors in the striatum and substantia nigra are critical for coordinating movement. Dysregulation can lead to disorders like Parkinson’s disease.
Reward and Motivation: D1, D2, and D3 receptors in the nucleus accumbens are involved in the brain’s reward pathways, influencing behaviors related to pleasure, addiction, and motivation.
Cognition and Memory: D1 and D4 receptors in the prefrontal cortex and hippocampus play roles in cognitive functions, attention, and memory.
Emotional Regulation: D3 and D4 receptors in the limbic system, including the hypothalamus and amygdala, are involved in emotional processing and regulation.
Hormonal Control: D2 and D5 receptors in the hypothalamus and pituitary gland regulate hormone secretion and maintain homeostasis.
Dopamine which receptors gives us pleasure and where are they located
Location and Function of Dopamine Receptors in the Reward Pathway
The reward pathway involves several key brain regions, and dopamine receptors play distinct roles within these areas. The primary regions include the nucleus accumbens, ventral tegmental area (VTA), and prefrontal cortex. Here, I will clarify the postsynaptic locations and functions of dopamine receptors involved in pleasure and reward:
- Nucleus Accumbens (NAc):
D1 Receptors:
Location: Postsynaptic neurons in the nucleus accumbens.
Function: Activation of D1 receptors enhances excitatory signaling, promoting the feeling of reward and pleasure.
D2 Receptors:
Location: Postsynaptic neurons in the nucleus accumbens.
Function: While D2 receptors are generally inhibitory at the cellular level, their activation in the nucleus accumbens helps fine-tune the reward response, contributing to the sensation of pleasure by modulating neuronal activity to prevent overstimulation. - Ventral Tegmental Area (VTA):
D2 Autoreceptors:
Location: Presynaptic neurons in the VTA.
Function: Regulate dopamine release through negative feedback, controlling the amount of dopamine that reaches downstream targets like the nucleus accumbens.
D1 and D2 Receptors:
Location: Postsynaptic targets of VTA dopamine neurons.
Function: Influence the activity of the neurons receiving dopaminergic inputs, playing a role in the overall reward processing. - Prefrontal Cortex (PFC):
D1 Receptors:
Location: Postsynaptic neurons in the prefrontal cortex.
Function: Enhance cognitive functions related to decision-making, planning, and working memory, which are indirectly related to the processing of reward.
D2 Receptors:
Location: Postsynaptic neurons in the prefrontal cortex.
Function: Modulate cognitive processes and influence the overall experience of reward and pleasure.
Other Dopamine Receptors Involved in Pleasure:
D3 Receptors:
Location: High concentrations in the limbic areas such as the nucleus accumbens, hypothalamus, and olfactory tubercle.
Function: Involved in the regulation of mood, motivation, and reward-related behaviors. D3 receptors play a significant role in the modulation of the reward system and are associated with addictive behaviors.
D4 Receptors:
Location: Frontal cortex, amygdala, hippocampus, and hypothalamus.
Function: Influence cognitive functions, emotional regulation, and reward processing. D4 receptors are implicated in attention and emotional responses related to reward.
Summary:
D1 Receptors:
Postsynaptic Locations: Nucleus accumbens, prefrontal cortex.
Role in Pleasure: Enhance excitatory signaling, promoting the feeling of reward and pleasure.
D2 Receptors:
Postsynaptic Locations: Nucleus accumbens, prefrontal cortex.
Role in Pleasure: Modulate neuronal activity to fine-tune the reward response, preventing overstimulation and contributing to the sensation of pleasure.
D3 Receptors:
Postsynaptic Locations: Limbic areas such as the nucleus accumbens and hypothalamus.
Role in Pleasure: Regulate mood, motivation, and reward-related behaviors.
D4 Receptors:
Postsynaptic Locations: Frontal cortex, amygdala, hippocampus, and hypothalamus.
Role in Pleasure: Influence cognitive functions, emotional regulation, and reward processing.
These receptors, through their various locations and mechanisms, collectively contribute to the complex experience of pleasure, motivation, and reward, playing crucial roles in both normal functioning and disorders related to the dopaminergic system.
