11- Signalling Between Cells 2 Flashcards
(24 cards)
Give examples of ionotrophic receptors
Nicotonic Acetylcholine
GABAa
Describe nicotonic acetylcholine receptors
Nicotinic Acetylcholine Receptor is located on skeletal muscle at neuromuscular junctions - it begins the depolarisation which leads to muscle contraction
• Nicotinic Acetylcholine Receptors can be found in the brain as well.
Describe GABA receptors
Located on many cells in the CNS
Allows transmission of anions
GABA binds to the receptor and causes the opening of the pore which allows an influx of chloride ions
GABA acting on cells will cause a depression of activity
If you block the GABA receptor you get hyperexcitability of the CNS and possibly epileptic seizures
Describe a G protein
• G-protein exists as a heterotrimer
• Trimer = alpha, beta and gamma subunits (GDP is NOT part of the heterotrimer)
• Beta and Gamma do NOT dissociate
• G-protein coupled receptors are also known as serpentine receptors and 7-TM
receptors (crosses the membrane 7 times - ‘7 transmembrane’)
• Heterotrimer isn’t attached to the G-protein receptor to begin with
Describe signal transduction in g coupled receptors
Ligand binds and changes conformation of the receptor
G-protein heterotrimer binds to the internal compartment of the G- protein coupled receptor
GDP is exchanged for GTP
GTP provides energy for the alpha and beta-gamma subunits to dissociate The subunits go and bind to their target proteins
Once the alpha subunit has attached to the target protein, internal GTPase activity within the subunit causes the GTP molecule to change to a GDP molecule
This allows the alpha subunit to unbind from the target protein and reform the heterotrimer with GDP attached
Describe a Gs protein linked receptor
Stimulates adenylate cyclase Adenylate cyclase converts ATP to cAMP
cAMP increases levels of PKA (protein kinase A)
EXAMPLE: β1-adrenergic receptor NOTE: beta blockers act on the β1- adrenergic receptor
Describe a Gi linked receptor
Inhibits adenylate cyclase thus reducing levels of cAMP and PKA EXAMPLE: M2-muscarinic receptor
Describe a Gq linked receptor
Activates phospholipase C (PLC) PLC converts PIP2 —-> IP3 + DAG 2+ IP3 —> increase in intracellular Ca DAG - activates PKC
• EXAMPLE: AT-1 angiotensin receptor
Angiotensin is a hormone produced in the kidneys which is the most potent vasoconstricter in the body
It causes vasoconstriction by acting on the Gq protein linked AT-1 receptor which causes smooth muscle contraction and, subsequently, vasoconstriction.
Describe the 3 types of g coupled receptors
Gs proteincoupledreceptors
Their target protein is adenylate cyclase, which is responsible for the conversion of ATP into cAMP. cAMP is converted into PKA which activates other enzymes in a cascade effect. Gs proteins stimulate adenylate cyclase
o Gi proteincoupledreceptors
Their target protein is also adenylate cyclase, but they inhibit its action
o Gq proteincoupledreceptors
Their target protein is phospholipase C (PLC), which breaks down PIP2 into IP3 and DAG. These have cascade effects of their own
Describe β2 adrenergic receptors
Gs subunit
Ligand: Noradrenaline
Location: Cardiac tissue
Physiological effect: Increase heart rate and force of contraction
Pharmacology: Beta blockers (e.g. propranolol, atenolol) used in the treatment of angina, arrhythmias, hypertension
describe D1 dopaminergic receptors
Gs subunit type
Ligand: Dopamine
Location: Neuronal
Physiological effect: Striatal growth, motor activity
Pharmacology: Some of the effects of chlorpromazine (anatagonist used in the treatment of schizophrenia) can be attributed to these receptors
Describe α2 adrenergic receptors
Gi subunit
Ligand: Noradrenaline
Location: Blood vessels
Physiological effect: Vasodilation and decreased force of contraction
Pharmacology: Agonists of this receptor (e.g. xylometazoline) are used as nasal decongestants
Describe ETA receptors
Gq subunit Ligand: Endothelin 1 Location: Blood vessels Physiological effect: Vasoconstriction Pharmacology: Agonists of this receptor (e.g. Ambrisentan) are used in the treatment of pulmonary arterial hypertension
Describe AT 1 receptors
Ligand: Angiotensin
Location: Blood vessels, adrenal cortex
Physiological effect: Vasoconstriction
Pharmacology: Blockers (e.g. Losartan) are used for the treatment of hypertension, heart failure and diabetic nephropathy
Describe the general mechanism of a enzyme linked receptor
The ligand binds to the receptor, resulting in receptors clustering
This activates enzyme activity within the cytoplasmic domain
The enzymes phosphorylate the receptor
This leads to binding of signalling proteins to the cytoplasmic domain
These signalling proteins recruit other signalling proteins and a signal is generated within the cell
The signal is terminated when a phosphatase dephosphorylates the receptor
What are the majority of enzyme linked receptors
The majority (98%) of enzyme linked receptors are tyrosine kinase linked receptors. However, there are other types, such as guanylate cyclase linked receptors and serine/threonine kinase receptors
Give 2 examples of tyrosine kinase linked receptors
Insulin receptor (CD220)
Ligand: Insulin
Location: Adipocytes, skeletal muscle
Physiological effect: Glucose uptake
Pharmacology: Subcutaneous insulin is given as a treatment of type II diabetes
ErbB receptor
Ligand: Epidermal growth factor, transforming growth factor β
Location: Ubiquitous
Physiological effect: Tumour genesis
Pharmacology: The HER 1 inhibitors (e.g. Panitumunab) are used to treat metastatic colorectal cancer
Give an examples of Guanylyl cyclase linked receptors:
NPRA
Ligand: Atrial/Brain natriuretic peptide
Location: Blood vessels
Physiological effect: Vasodilation; decreasing blood pressure Ser/
What is intracellular signal transduction?
Intracellular receptors are acted upon by molecules that can diffuse through the cell membrane and so need to be lipid soluble. This includes steroid hormones
The receptor acts as a transcriptional factor. The ligand is needed to activate it
Describe type 1 intracellular signal transduction
Located within the cytoplasm
Attached to heat shock proteins
Ligands are usually STEROIDS which pass through the membrane and act on intracellular receptors
Ligand binds to the Type 1 receptor which dissociates from the heat shock protein
The ligand and receptor move together to the nucleus
It binds to the DNA and causes increased or decreased TRANSCRIPTION
Describe type 2 intracellular signal transduction
Located within the nucleus and is already bound to DNA
Ligand comes in, moves through the nuclear envelope and binds to the receptor on the DNA causing changes in transcription
Give a type 1 IST example
Glucocorticoid receptor
Ligands: Cortisol, corticosterone
Location: Intracellular, wide distribution
Physiological effect: ↓ immune response, ↑Gluconeogenesis
Pharmacology: The glucocorticoids (e.g. Prednisolone) are used in the treatment of inflammatory disorders, asthma, rheumatic disease, cancer and many other conditions
Give a type 2 IST example
Thyroid hormone receptor
Ligand: Thyroxine (T4), triiodothyronine (T3)
Location: Nuclear, wide distribution
Physiological effect: Growth and development
Pharmacology: The thyroid hormones (e.g. Levothyroxine) are used to treat hypothyroidism, goitre & thyroid carcinoma
Give and example of Ser/Thr kinase linked receptor
EXAMPLE: TβR1
• Ligand: Transforming Growth Factor β
• Physiological effect: apoptosis
