Pharmacology Flashcards
Why must cells communicate
to coordinate complex activities
Explain specificity of intercellular signals
Chemical signals released from one cell produces a response only in those cells that express the right receptor. Different receptors for the same chemical signals can produce different responses in different cells - allows for specificity: the right response from the right cells
What can intercellular signalling molecule response include
Changes in:
* Secretory activity
* contractile activity
* metabolism
* membrane permenbility
* rate of proliferation or differentiation
What is the process of intercellular communication also called
signal transduction
What does the process of intercellular communication depent on
not sure if need to know
a range of receptors
Why are there 2 different types of receptor
- Intracellular receptors - lipophilic molecules which can diffuse directly through lipid bilayer (e.g. hormones)
- Cell surface receptors - hydrophilic signalling molecules, signal tranduced across membrane
Explain the action of lipidphilic (soluble) signalling molecules
- Dissolve through lipid bilayer of plasma membrane
- Bind to intacellular receptors in the cytosol (or nucleus)
- Reponse is triggered
Give NO and steroid hormones as examples of lipophilic signalling molecules
- NO (nitric oxide): binds to soluble guanylyl cyclase in the cytosol. Generates cGMP as a 2nd messenger that regulates cell activity
- Steroid hormones: recepotr is often transcription factor that regulats transcription in the nucleus
What are examples of primary messengers (1st)
neurotransmitters and hormones
Where must hydrophilic signalling molecules bind and how many are there?
To receptors on the cell surface: 4
Name all 4 types of cell surface receptor
- Receptor-channels
- G protein-coupled receptors (GPCRs)
- Receptor-enzymes
- Integrin receptors
3/4 are both catalytic receptors
Explain each of the 4 types of cell surface receptor
- Receptor-channels - also called ionotropic receptors and ligand binding opens/closes channel e.g. nicotinic acetylcholine receptors
- G protein-coupled receptors (GPCRs) - aka metabotropic receptors and do all their work via a middle man (G protein) which regulates enzyme activity/opens ion channel when ligand binds
- Receptor-enzymes - receptors with intrinsic enzyme activity (insulin receptors) or which are bound to an enzyme (cytokine receptors) - ligand binding to receptor-enzyme activates an intracellular enzyme
- Integrin receptors - receptors that interact with the cytoskeleton - ligand binding alters enzymes or the cytoskeleton
What will different G-protein couple to in GPCRs
different 2nd messenger systems
What could a G protein couple to in GPCRs
3
- Direct to ion channels: affects membrane potential and firing of action potentials (opens/closes ion channels)
- Adenylyl cyclase: produces cAMP as 2nd messenger after breaking down ATP. Regulates protein kinase A activity ( which phosphorylates target protiens and changes their activity)
- Phospholipase C: produce IP3 and DAG as 2nd messengers, releases Ca2+ and regulates protien kinase C activity. Phosphorylates target protiens and changes their activity
What does the phosphorylation of myosin by adenylyl cyclase pathway (GPCR) lead to?
smoother muscle contraction
Sources of Calcium
3
- Internal stores via IP3 - or Ca2+ - stimulated release Ca2+ from ER
- From outside the cell via voltage or ligand-gated Ca2+ channels - need neurotransmitter?
- Via inhibition of Ca2+ transport out of the cell
What G-protein messenger system release Ca2+
(and regulates protien kinase C activity)
Phospholipase C: produce IP3/DAG as 2nd messengers
What are the effects of Ca2+ in the cell
- Directly affect target protein (e.g. PKC)
- Bind to calmodulin which then activates target protein (e.g. Ca2+ - calmodulin dependent kinase - CamKinase)
- Works via some other Ca2+ binding protien (e.g. troponin)
How is intercellular signalling achieved
chemical signalling molecules acting on specific receptors
What are receptors and their intracellular signalling pathways at the site of action of?
Drugs
What can pharmacological agents be
- Endogenous - made by body (e.g. neurotransmitters and hormones)
- Exogenous - e.g. drugs
Define drug and give examples of possible sources
Any chemical agent that affects a biological system
Sources inc: natural products (from plants), synthetic drugs, biotechnology useing living systems (insulin) to make therapeutic agents, gene therapy
How do drugs act
by interacting with a binding receptor
Give 6 examples of receptors
- Cell surface receptors (B-adrenergic receptors)
- Intracellular receptors (steroid receptors)
- Ion channels (TTX blocks Na+ channels)
- Carriers (ouabain inhibits na/k ATPase)
- Enzymes (asprin/ibuprofen inhibit cyclooxygenase)
- nucleic acids (tumor promoters bind to DNA)
What happens greater the number of drug particles there are (whilst still less than total no. of receptors)
Size of response will inc, as more drugs bind to receptors which each produce an individual response
What happens one there is more drug than receptors
Maximum (saturated) response is reached, where dose can’t inc any more
Define EC50
Half maximal effective concentration is a measure of the concentration of a drug, antibody or toxicant which induces a response halfway between the baseline and maximum after a specified exposure time. - dose required to give 50% of response
How is (drug) affinity determined
by the strength of chemical attraction between drug and receptor
What does a low EC50 indicate
a high affinity
What does it mean if a lower [drug] is needed to intiate the same response (proportionally)
That drug has a higher affinity
What graph can be used to determine drug affinity
Concentration response/dose curves
Efficacy
How “good” a drug is at activating the receptor - the maximum response that can be achieved with a drug
How do fully and partially activated receptors look on a conc response curve
see sheet: Efficay of partially activated receptor less so therefore, response (y-axis) not so great
What does the size of a drug response depend on?
- Drug affinity - does it bind?
- Drug efficacy - does it activate receptor?
this determines the properties of the drug
What do agonists and antagonists do?
- Agonists: mimic normal effect of receptor
- Antagonists: block normal action of receptor
Give the affinity and efficay for:
* Full agonist
* partial agonist
* antagonist
- Full agonist A=high E=high
- Partial agonist A=high E=mid
- Antagonist A=high E=low (blocks receptor)
How are antagonists useful in terms of physiological responses
If don’t want response, anatagonists compete with endogenous agonists to bind with receptor. If greater [antagonist] then physiological response is blocked
How can we overcome competitive agonists
Inc sub conc
Which way is the agonist conc-response curve shifted in the prescence of a competitive antagonist
To the right - higher [agonist] required to overcome competitive antagonist inhibition
non-competitive antagonist
stop receptor working by binding to a different site to the agonist - conc-response curve different
What doesn’t EC50 explain
efficacy - only explains affinity
What may one signalling molecule act on
several receptor subtypes
Selective agonists
theraputic potential
drugs that activate only some of those receptors
e.g. salbutamol (B2 agonist)
selective antagonist
theraputic potential
drugs that block only some of those receptors
propranolol (B1 and B2 antagonist)
Explain how one signalling molecule can have multiple receptors
Shape of molecule means it can fit into multiple receptors (lock and key)
How can some drugs be selective in binding to receptors
Can bind to, and activate only some receptors
or not activate in the case of selective antagonists
in conclusion, what can the effect of drugs/endogenous signallingmolecules have on the body
neurotransmitter/hormone etc. can bind to different receptors in different parts of the body and** produce different responses**
What are some common receptors (adrenaline/noradrenaline)
a1, a2, B1, B2 adrenergic recptors
define receptor
molecules that recieves a stimulus
