Nature Of Receptors Flashcards
The nature of receptors was an hypothesis T/F
True
Functions of receptors are determined by the interaction of
lipophillic or hydrophillic domains of the peptide chain within the drug molecule.
Non-polar hydrophobic portion of the amino acid(receptor)______________________while polar hydrophilic remain on cell surface.
remain buried in membrane
hydrophilic drugs cannot cross the membrane and has to bind with
the polar hydrophilic portion of the peptide chain of receptor
All four major families of receptors have common properties but individual receptors
have different amino acid sequencing.
Binding of polar drugs in ligand binding domain induces conformational changes (
alter distribution of charges and transmitted to coupling domain to be transmitted to effector domain.
Subtypes of nicotine receptors
Nn : neuronal
Nm: muscle
Subtypes of muscarinic receptor
M1
M2
M3
M4
M5
5 criteria for classifying receptors
Pharmacological criteria
Tissue distribution
Ligand binding
Transducer pathway
Molecular cloning
Pharmacological criteria is the _______ & ___________ approach.
It’s based on?
Examples include
classical
oldest
The potencies of selective agonist and antagonists
Eg Muscarinic, nicotinic, alpha and beta adrenergic etc.
I’m tissue distribution, what is the basis for the subtype
The _______________ receptor is beta 1
____________________ is beta 2
the relative organ or tissue distribution is the basis for designating the subtype
cardiac beta adrenergic
bronchial beta adrenal receptor/ adrenoreceptor
Ligand binding: Measurement of specific binding of high affinity _________________ to _________________ (usually membranes) in ________ and its selective displacement by various selective ____________\_________is used to delineate receptor subtype. E.g. multiple __________ receptors were distinguished by this approach.
Radio labeled Ligand (radioactive substance used for research)
Cellular fragments
In vitro (Petri dish)
Agonists/ antagonists
5-HT (hydroxytryptamine / serotonin)
In Transducer pathway, receptor subtype may be distinguished by?
e.g. M cholinergic receptor acts through?
while N cholinergic receptor?
the mechanism through which their activation is linked to the response,
G proteins
Gates Influx of Na+ ions
In Molecular cloning, the receptor protein is cloned and its __________ as well as __________ is worked out. This approach has resulted in a flood of receptor subtypes and several isoforms, even in orphan receptors?
detailed amino acid sequence
as well as three dimensional structure
Receptors without known ligands
What are silent receptors?
They are also known as _______ or _______
Example is _______
These are sites which bind specific drugs but no pharmacological response is elicited
Drug acceptors or Sites of loss
e.g. plasma proteins
What are spare receptors
The remaining unoccupied receptors are just serving as receptor reserve because drug can produce the maximal response when even less than 1% of the receptors is occupied; and are called spare receptors.
What is upregulation?
Depletion of noradrenaline/ treatment with adrenergic antagonists results in?
administration of β-blocker causes?
The increase in the number of receptors with subsequent increase in receptor sensitivity)
supersensitivity of tissues to noradrenaline & increased in receptor no.
an increase in adrenergic receptor
What is down regulation
Due to continued exposure to a drug/ agonist: It results in blunted response which is?
Repeated administrations of adrenergic agonists in asthma leads to
reduction in the number of receptors available for activation & reduced affinity to drug reduced no. of receptors
Desensitisation/ refractoriness/ tolerance
down regulation of beta receptors
Diseases linked to receptor malfunction are of 2 major types
- Autoantibodies directed against receptor proteins
Eg: Myasthenia gravis
- Mutations in genes encoding receptors and proteins involved in signal transduction.
Eg
Mutations of genes encoding GPCRs: hypoparathyroidism, cancers
What happens in Myasthenia Gravis
autoantibodies that inactivate nicotinic acetylcholine receptors.
Myasthenia gravis (MG) is a disease of the postsynaptic neuromuscular junction (NMJ) where nicotinic acetylcholine (ACh) receptors (AChRs) are targeted by autoantibodies.
Autoantibodies can also mimic the effects of agonists, as in many cases of
thyroid hypersecretion, caused by activation of thyrotropin receptors
What happens in insulin resistance
Having fewer insulin receptors or less than expected receptor response upon insulin stimulation
Testicular feminization
TF or Androgen insensitivity syndrome (AIS) occurs when someone is genetically male but receptor is insensitive to androgens (male sex hormones).
This means the person has male sex chromosomes (one X and one Y chromosome) but may have female genitals.
Familial hypercholesterolemia involves
Familial hypercholesterolemia is caused by a reduction or defect in the LDL receptor, that result in reduced LDL-receptor activity and defective clearance of lipoproteins from the circulation.
This causes, on average, a twofold increase in plasma LDL-cholesterol concentration
People with FH have increased blood levels of low-density lipoprotein (LDL) cholesterol, sometimes called “bad cholesterol
