Drug Action II Exam I: Metabotropic and Ionotropic Receptors

_________: a receptor protein that formspart of a ligand-gated ion channel, so that binding ofligand (e.g. a hormone or neurotransmitter) to thereceptor causes opening of the channel, permitting ionsto flow through it.

Ionotropic receptor

Ionotropic receptors allow different kinds of ____ to travel in and out of the cell

ions

When a ligand binds to an ionotropic receptor what happens?

a conformational change that allows the channel to change shape and open for ions

Iontropic receptors are also called?

Ligand -gated transmembrane ion channels

What ions generally travel through ionotropic receptors?

K+, Na+, Cl-, Ca+2

Are ionotropic receptors fast or slow? Do they open or close quickly?

fast, yes they open and close fast because the ligand doesn't stay in place long

________: a type of membrane-bound receptor in cells that activates a second messenger which then induces a cellular response

Metabotropic receptor

When a metabotropic receptor is activated, a series of intracellular events are triggered that can also result in ________ opening.

ion channels

Activation of _______ receptors can involve a wide range of second messenger signaling

metabotropic receptors

_______: synaptic receptors located primarily on the membranesof neuronal cells

Glutamate receptors

______: is abundant in the human body, but particularly in the nervous system and especially prominent in the human brain where it is the body's most prominent neurotransmitter, the brain's main excitatory neurotransmitter

Glutamate

What is the brains main excitatory NT?

Glutamate

Glutamate receptors are responsible for the _______________ of neural cells

glutamate-mediated postsynaptic excitation

Glutamate is important for _______, ______, ______, and ______

neural communication, Memory formation, Learning, regulation

______ receptors are implicated in a number of neurological conditions

glutamate

Glutamates central role in _____ and prevalence in the _________ has been linked to many neurodegenerative diseases

EPSP, central nervous system

T/F glutamate is linked the gene mutations

true

The ionotropic glutamate receptors comprise members of the ________, ___________, and ________ receptor classes, named originally according to their preferred synthetic agonist.

NMDA (N-methyl-D-aspartate), AMPA(α-amino-3-hydroxy-5-methyl-4-isoxazole proprionicacid) and kainate

The NMDA receptor channel commonly has a high relative permeability to ____ and _____ and is blocked by _____

Ca+2, Na+, Mg+2

Activation of the NMDA receptor by _______ induces removal of mg+2 and the opening of the ion channel

glutamate

Why is NMDA-R unique?

because its activation requires simultaneous binding of 2 different agonist (glu and gly) and also contains binding sites for ketamine and phencyclidine (PCP)

NMDA-R contains binding sites for _______ and ________ that act as noncompetitive antagonists to cause cognitive impairment and hallucinations.

ketamine and phencyclidine (PCP)

______: dysfunction associated with epilepsy andHuntington's disease, autism and schizophrenia, while function in normal patients is unclear

Kainate-R

________: show promise as neuroprotective agentfor treatment of stroke

AMPA-R antagonist

_______: a type of glutamate receptor that are G-protein-coupled receptors (GPCRs)

Metabotropic glutamate receptors (mGluRs)

T/F mGluRs dont have to bind to glutamate

False they do

Hyperactive pathological conditions associated with glutamate neuronal dysfunction

-Schizophrenia and psychosis.

-Neurotoxicity associate with stroke.

-Antagonist are neuroprotective in Parkinson's and Alzheimer's disease

Hypoactive pathological conditions associated with glutamate neuronal dysfunction

-Depression

-Cognitive impairments

What is ionotropic Gaba receptors endogenous ligand?

y-aminobutyric acid (GABA)

_____: the major inhibitory neurotransmitter (produces an IPSP) inthe central nervous system

y-aminobutyric acid (GABA)

Upon activation, the GABAA receptor selectively conducts ____ through its ion channel, resulting in ____________ of the neuron. This causes an inhibitory effect on neurotransmission by diminishing the chance of a successful action potential occurring.

Cl-, hyperpolarization

When GABA is activated what is the overall effect?

inhibitory effect on neurotransmission by diminishing the chance of a successful action potential occuring

When GABA is activated and Cl- travels through the ion channel it results in _______________ of the neuron

hyperpolarization

____________: are metabotropic trans-membrane receptors for gamma-aminobutyric acid (GABA) that are GPCR that ultimately lead to the opening of potassium channels to induce an IPSP.

GABAb receptors

GABAb receptors lead to the opening of __________ channels to indue a ______

potassium, IPSP

The changing potassium concentrations ________ the cell at the end of an action potential

hyperpolarize

________ is a G-protein coupled receptor that enhances K+ channel conductance

GABAb

Clinical conditions related to GABA neuronal dysfunction:

-Movement Disorders: Parkinson's and Huntington's disease

-Spasticity: antispasmodics and muscle relaxants

-Epilepsy: anti-seizure drugs

-Sleep Disorder

-Psychosis/Anxiety: Reductions in GABA activity associate with thought and emotional disorders.

-Alcoholism/ Addictions

Ligand-gated sodium channels are activated by the binding of a ligand instead of a change in __________

membrane potential

Acetylcholine ionotropic Na+ receptors are found in the __________ as nicotinic receptors, where the ligands are _______ molecules

neuromuscular junction, acetylcholine

Instead of becoming an ion channel for sodium, muscarinic receptors are _______

GPCR

With muscarinic receptors ___ binds to the receptor which allows a change in the proteins shape that allows it to phosphorylate or activate various second messengers

Ach

_________ are G-protein coupled receptors that can be stimulatory (M1) or inhibitory (M2)

Muscarinic receptors

What are examples of therapeutics that use cholinergic antagonists (nicotinic)?

Nicotinic antagonist:

• Ganglionic blocker to treat hypertension (hexamethonium)

• Neuromuscular blocker used as muscle relaxants (atracurium)

• Antitussives (dextromethorphan)

What are examples of therapeutics that use cholinergic agonists (nicotinic)?

Nicotinic agonists:

• Used to treat tobacco dependence (Chantix)

• Treatment of dementia (Reminyl)

• Treatment of glaucoma (Miostat)

What are examples of therapeutics that use cholinergic agonists (muscarinic)?

Muscarinic agonist:

• M1 agonist used to improve cognitive function in Alzhemimer's

• M3 agonist used to treat glaucoma and dry mouth syndrome

What are examples of therapeutics that use cholinergic antagonists (muscarinic)?

Muscarinic antagonist:

• Treat bradycardia (atropine)

• Antispasmodic in GI tract (scopolamine)

• Asthma (atrovent)

• Decreases tremor associated with Parkinson's disease.

• Incontinence

What type of membrane receptor is insulin receptors?

transmembrane

______ and _____ activate insulin receptors (IR)

IGF-I, IGF-II

Insulin receptors (IR) belong to the large class of __________ receptors

tyrosine kinase

Many drugs are insulin analogues that activate the IR to (decrease/increase) glucose uptake from blood

increase

Some drugs decrease liver ___________ (metformin)

gluconeogenesis

Some drugs act as __________ to mimic post-receptor IR down-stream signaling (glitazones)

transcription factors

_________ induce an increase secretion of endogenous insulin.

sulfonylureas

______: inhibitors block glucose uptake in renal tubules

SGLT-2

DDP-4 inhibitors ______ insulin secretion and ________ glucagon secretion

increase, decrease

_______: When activated can induce an EPSP(excitatory) or inhibitory (IPSP) response

Serotonin receptors (5HT)

How many 5HT receptors are GPCRs?

12

_________ is coupled to inhibitory proteins, whereas 5HT ___, ___, ___ and __ and coupled to stimulatory G-proteins

5HT1,

2,4,6,7