Cholinergic receptors

43,999views

Cholinergic receptors

Pharmacology

Pharmacology

Introduction to pharmacology
Enzyme function
Pharmacodynamics: Drug-receptor interactions
Pharmacodynamics: Agonist, partial agonist and antagonist
Pharmacodynamics: Desensitization and tolerance
Pharmacokinetics: Drug absorption and distribution
Pharmacokinetics: Drug metabolism
Pharmacokinetics: Drug elimination and clearance
Drug administration and dosing regimens
Selective serotonin reuptake inhibitors
Serotonin and norepinephrine reuptake inhibitors
Tricyclic antidepressants
Monoamine oxidase inhibitors
Atypical antidepressants
Typical antipsychotics
Atypical antipsychotics
Lithium
Nonbenzodiazepine anticonvulsants
Anticonvulsants and anxiolytics: Barbiturates
Anticonvulsants and anxiolytics: Benzodiazepines
Androgens and antiandrogens
Estrogens and antiestrogens
Progestins and antiprogestins
Aromatase inhibitors
Uterine stimulants and relaxants
Pulmonary corticosteroids and mast cell inhibitors
Hyperthyroidism medications
Hypothyroidism medications
Adrenergic receptors
Cholinergic receptors
Cholinomimetics: Direct agonists
Muscarinic antagonists
Cholinomimetics: Indirect agonists (anticholinesterases)
Sympathomimetics: Direct agonists
Sympatholytics: Alpha-2 agonists
Adrenergic antagonists: Presynaptic
Adrenergic antagonists: Alpha blockers
Adrenergic antagonists: Beta blockers
ACE inhibitors, ARBs and direct renin inhibitors
Thiazide and thiazide-like diuretics
Calcium channel blockers
cGMP mediated smooth muscle vasodilators
Class I antiarrhythmics: Sodium channel blockers
Class II antiarrhythmics: Beta blockers
Class III antiarrhythmics: Potassium channel blockers
Class IV antiarrhythmics: Calcium channel blockers and others
Lipid-lowering medications: Statins
Lipid-lowering medications: Fibrates
Miscellaneous lipid-lowering medications
Hypoglycemics: Insulin secretagogues
Insulins
Miscellaneous hypoglycemics
Adrenal hormone synthesis inhibitors
Mineralocorticoids and mineralocorticoid antagonists
Antihistamines for allergies
Acid reducing medications
Laxatives and cathartics
Antidiarrheals
Anticoagulants: Heparin
Anticoagulants: Warfarin
Anticoagulants: Direct factor inhibitors
Antiplatelet medications
Thrombolytics
Hematopoietic medications
Ribonucleotide reductase inhibitors
Topoisomerase inhibitors
Platinum containing medications
Anti-tumor antibiotics
Microtubule inhibitors
DNA alkylating medications
Monoclonal antibodies
Antimetabolites for cancer treatment
Glucocorticoids
Protein synthesis inhibitors: Aminoglycosides
Antimetabolites: Sulfonamides and trimethoprim
Antituberculosis medications
Miscellaneous cell wall synthesis inhibitors
Protein synthesis inhibitors: Tetracyclines
Cell wall synthesis inhibitors: Penicillins
Miscellaneous protein synthesis inhibitors
Cell wall synthesis inhibitors: Cephalosporins
DNA synthesis inhibitors: Metronidazole
DNA synthesis inhibitors: Fluoroquinolones
Mechanisms of antibiotic resistance
Integrase and entry inhibitors
Nucleoside reverse transcriptase inhibitors (NRTIs)
Protease inhibitors
Hepatitis medications
Non-nucleoside reverse transcriptase inhibitors (NNRTIs)
Neuraminidase inhibitors
Herpesvirus medications
Azoles
Echinocandins
Miscellaneous antifungal medications
Anthelmintic medications
Antimalarials
Anti-mite and louse medications
Acetaminophen (Paracetamol)
Non-steroidal anti-inflammatory drugs
Opioid agonists, mixed agonist-antagonists and partial agonists
Antigout medications
Osteoporosis medications
Migraine medications
General anesthetics
Local anesthetics
Neuromuscular blockers
Anti-parkinson medications
Medications for neurodegenerative diseases
Opioid antagonists
Osmotic diuretics
Carbonic anhydrase inhibitors
Loop diuretics
Potassium sparing diuretics
PDE5 inhibitors
Bronchodilators: Beta 2-agonists and muscarinic antagonists
Bronchodilators: Leukotriene antagonists and methylxanthines
Arsenic poisoning
Cyanide poisoning
Lead poisoning
Methemoglobinemia
Ethylene glycol poisoning
Mercury poisoning
Paracetamol toxicity
Serotonin syndrome
Neuroleptic malignant syndrome
Medication overdoses and toxicities: Pathology review
Environmental and chemical toxicities: Pathology review

Transcript

Watch video only

Cholinergic receptors are receptors on the surface of cells that get activated when they bind a type of neurotransmitter called acetylcholine.

There are two types of cholinergic receptors, called nicotinic and muscarinic receptors - named after the drugs that work on them.

The nervous system is divided into the central nervous system, so the brain and spinal cord, and the peripheral nervous system, which includes all the nerves that connect the central nervous system to the muscles and organs.

The peripheral nervous system is divided into the somatic nervous system, which controls skeletal muscles, and the autonomic nervous system, which is further divided into the sympathetic and the parasympathetic, and controls internal organs.

Neurons are the main cells of the nervous system. They’re composed of a cell body, which contains all the organelles, and nerve fibers, which are projections that extend out from the neuron cell body.

Nerve fibers are dendrites that receive signals from other neurons, and axons that send signals along to other neurons.

Where two neurons come together is called a synapse; that’s where an axon releases neurotransmitters that bind to receptors present on the cell membrane of the dendrites or the cell body of the next neuron in the series.

Now the autonomic nervous system - so both sympathetic and parasympathetic - is made up of a relay that includes two neurons: preganglionic neurons, which have their cell bodies in nuclei throughout the spinal cord, and postganglionic neurons, which have their cells bodies in ganglia out of the spinal cord.

Axons of preganglionic neurons exit the spinal cord to reach the ganglia and synapse with postganglionic neurons. Then, the axons of postganglionic neurons exit the ganglia to reach the organs and synapse with the target organ cells.

Let’s zoom into the synapses. In the sympathetic nervous system, preganglionic and postganglionic neurons release different neurotransmitters.

Preganglionic neurons release the neurotransmitter acetylcholine, which binds to nicotinic receptors on the cell membrane of postganglionic neuron cell bodies.

And most postganglionic neurons release the neurotransmitters adrenaline and noradrenaline, collectively called catecholamines.

These catecholamines bind to adrenergic receptors on the plasma membrane of the target organ cells.

A few sympathetic postganglionic neurons release acetylcholine, which binds to muscarinic receptors on target organ cells.

Now for the parasympathetic nervous system, both preganglionic and postganglionic neurons release acetylcholine.

The acetylcholine released by preganglionic neurons binds to nicotinic receptors on postganglionic neuron cell bodies.

Then, the postganglionic neurons release acetylcholine, but in this case it binds to the muscarinic receptors on the target organ cells.

In the somatic nervous system, the site where a motor neuron axon comes into contact with a skeletal muscle fiber is called a neuromuscular junction.

Whenever a motor neuron receives an electrical impulse from the brain, this triggers the release of small vesicles that contain acetylcholine into the neuromuscular junction.

Acetylcholine then binds to the nicotinic receptors on skeletal muscle cells, and triggers skeletal muscle contraction.

Now, nicotinic receptors are also called ionotropic acetylcholine receptors, because they are ligand gated ion channels, which means that they open when acetylcholine binds, allowing positively charged ions like sodium and potassium to flow through them.

Nicotinic receptors are made of five subunits, two alpha, one beta, one gamma, and one delta subunit, and together they form a tunnel that’s generally closed.

When acetylcholine binds to the alpha subunits, the tunnel changes shape and opens up. That lets sodium flow into the cell, and potassium out of the cell, following a passive gradient. This leads to depolarization of the cell, which is when the cell undergoes a shift in electric charge distribution and becomes more positive, triggering a cellular response.

Muscarinic receptors are also known as metabotropic acetylcholine receptors because they activate intracellular proteins when acetylcholine binds.

Muscarinic receptors are seven pass transmembrane receptors, which means they are really long proteins that have one end that sits outside the cell and binds acetylcholine, then the snake-like protein dips in and out of the cell membrane seven times, and finally ends on the inside of the cell.

The end of the protein within the cell activates intracellular proteins.

Sources

  1. "Medical Physiology" Elsevier (2016)
  2. "Physiology" Elsevier (2017)
  3. "Human Anatomy & Physiology" Pearson (2018)
  4. "Principles of Anatomy and Physiology" Wiley (2014)
  5. "Membrane potential depolarization decreases the stiffness of vascular endothelial cells" Journal of Cell Science (2011)
  6. "Highly fatal fast-channel syndrome caused by AChR   subunit mutation at the agonist binding site" Neurology (2012)
  7. "Cholinergic Modulation of Neuronal Excitability in the Accessory Olfactory Bulb" Journal of Neurophysiology (2010)
  8. "Muscarinic and Nicotinic ACh Receptor Activation Differentially Mobilize Ca2+ in Rat Intracardiac Ganglion Neurons" Journal of Neurophysiology (2003)