Physiology Flashcards
What are the four types of receptors?
Ligand Gated
G protein coupled
Tyrosine-kinase
Nuclear
What agonists work on ligand gated ion channels/
Neurotransmitter
Hormones
What is the difference between a neurotransmitter and a hormone?
They can be the same substance, neurotransmitters are released across synapse from a nerve.
What occurs after agonist binds to the ion channel?
Conformational change in structure.
Ions allowed to pass through membrane.
How quick is the response in ligand gated ion channels?
Milliseconds
How quick is the response in G protein coupled receptors?
Seconds
In a G protein coupled receptor describe the structure of the G proteins?
Alpha subunit attached to a GDP
Beta and Gamma subunits bound in a dimer
In B2 adrenoreceptor what. type of G protein is present?
Gs alpha
Upon binding of adrenaline to B2 adrenoreceptor what occurs?
Conformational change of the receptor.
GDP is swapped for charged GTP on the alpha subunit.
Alpha subunit breaks away and binds to adenyl cyclase
What does adenyl cyclase do?
Converts ATP to cAMP
What is cAMP?
A cell signalling molecule?
In B2 adrenoreceptors what does an increase intracellular cAMP do?
PKA is activated
Inhibits MLCK activity
Bronchodilation
In G coupled protein receptors why does the reaction stop?
Weak bond between agonist and receptor.
GTP is hydrolysed breaking bond between alpha submit and adenyl cyclase
In A2 adrenoreceptors what is the difference in adenyl cyclase?
Adenyl Cyclase is active before activation
What G protein alpha subunit is present in A2 adrenoreceptors?
Gi (Inhibits)
What occurs after agonistic binding to receptor in A2 adrenoreceptors?
Alpha subunit only
Alpha subunit is activated by GTP.
B
Alpha subunit binds to adenyl cyclase inhibiting it.
What occurs after agonistic binding to receptor in A2 adrenoreceptors?
Beta and Gamma subunits only
The dimer binds to K+ channels
Cell membrane becomes hyperpolarized
What is the resultant action upon A2 adrenoreceptor activation?
Smooth muscle relaxation especially in GI tract
In alpha 1 adrenoreceptors what G subunit is present
Gq
What does the activated alpha subunit do in A1 adrenoreceptors?
Activates phospholipase C
What is the function of phospholipase C in regards to A1 adrenoreceptors?
Converts PIP2 into DAG and IP3
What does an increase in intracellular DAG and IP3 result in?
Increase in intracellular Ca2+
Vasoconstriction
Where are A1 adrenorecpetors commonly present?
Within the vasculature
In regards to G coupled reactions what kind of response do they evoke?
Amplification a large reaction from smaller stimuli
In regards to Tyrosine Kinase what kind of response do they evoke?
Divergent reaction, lots of different responses from the same stimuli.
What are the agonists of tyrosine kinase receptors?
Hormones e.g. insulin
What is the structure of a tyrosine kinase receptor?
They are a dimer
Upon binding of the agonist to the tyrosine kinase receptor what occurs?
It undergoes a conformational change bringing the two pieces together.
Intracellular tyrosine molecules are activated by ATP (phosphorylated)
Relay proteins bind to tyrosine triggering different cellular responses.
What are relay proteins?
These are individual proteins which bind to the tyrosine molecules present on the intracellular extension of the receptor, each one triggers a different response within the cell.
How long is the response in tyrosine kinase receptors?
Up to a few hours
How many folds pass across the membrane in a G protein coupled receptor?
7 times
Autocrine regulation
Self limiting
Chemical released by the cell bind to receptors on the same cell
Example of autocrine regulation
Somatostatin released from D cells
Paracrine regulation
Chemicals released by cell bind to receptors on cells located proximally
Example of paracrine regulation
Somatostatin released by D cells binds to parietal cells to inhibit release of HCL
Both located in stomach
How is endocrine regulation divided?
Negative and positive feedback
Endocrine Regulation
Chemicals released by cells into the circulatory system where they travel and bind to receptors on target cells.
Example of endocrine regulation
Insulin released by B cell in pancreas and target cells in liver.
Negative feedback
Primary Mechanism of maintaining homeostasis by resisting fluctuations away from physiological set point.
Positive feedback
Initial stimuli initiates a response which exaggerates the initial change
Examples of positive feedback
Oxytocin in childbirth
Blood clot cascade
What makes up intrinsic regulation?
Autocrine and Paracrine
What makes up extrinsic regulation?
Nervous system and endocrine
Example of negative feedback ?
Cortisol stress cycle
Cortisol is the final product but high levels of cortisol inhibits ACTH and CRh production all of which are precursors.
What is the function of GLUT2 receptors?
Censorship of blood glucose levels
Allows diffusion of glucose into the B cells in the pancrease.
What enzyme is responsible for monitoring blood glucose and how does it complete its function?
Glucokinase
An enzyme responsible for glycolysis
Increased glucose increases ATP conc
As a result of high ATP levels in the B cells due to high glucose levels what happens?
ATP sensitive K+ channels close
Voltage Gated Ca 2+ channels open
Excretion of insulin via exocytosis
What is the structure of insulin?
Polypeptide dimer held together by disulphide bridges
How is insulin produced then activated
Produced in RER of B cell
Cleaved to form active form
What can be used to monitor inulin production?
C protein
A by product of the cleaving of insulin to form active enzyme
Describe insulin release
Its biphasic
1st phase is dependant on dose larger dose = larger spike
2nd phase smaller as vesicles need to be prepared
What is the 1st phase of insulin release called?
Readily Released Pool
Insulin already packaged in active vesicles so quick response
In type II diabetes what happens to the phases?
They weaken and flatten
Why in type II diabetes does the pattern of release change?
As glucokinase activity is downregulated
Why in type II if enough weight is lost can they symptoms of diabetes disappear?
As B cells still producing insulin however, Blood glucose concentration is higher than the KM of glucokinase so its working at capacity basically.
By loosing weight glucose conc can be brought below KM of glucokinase.
What kind of receptor are the ATP sensitive K+ channels?
Inward rectifier - ion channel
Contain a sulphonylurea receptor - regulatory unit
Octomeric structure - 8 subunits
What is the function of K+ ATP channels and what stimulates them?
They inhibit insulin release by preventing Ca2+ entry
Diazoxide
What are the two main thyroid hormones?
T4 and T3
What is T3
Tri-iodothyronine