Signalling Molecules Flashcards
(24 cards)
What does the term ‘pharmacology’ mean?
Study of molecular signals regulating physiological processes.
What are the different types of extracellular signals (based on distance of action)?
- Autocrine
- Paracrine
- Endocrine
What is autocrine signalling?
- Cells respond to signalling molecules they produce and release themselves.
- Typically act over microns.
- Shares many paracrine signalling molecules, e.g. Cytokines and growth factors.
What is paracrine signalling?
- Act on neighbouring cells - molecules released into extracellular environment and induce changes in receptor cells.
- Uses signals such as:
- Neurotransmitters
- Local chemical mediators
What is the function of neurotransmitters?
- Mediate signalling between neurons over synapses (20 nm distance, msecs transmission velocity).
- Electrochemical system as enables chemical signal conversion/coupling with electrical signals.
- Signalling can be:
- Excitatory - increases firing rate post-synaptically
- Inhibitory - decreases firing rate post-synaptically
What are the major groups of neurotransmitters?
- Amino acids
- glutamate
- glycine
- GABA
- Monoamines
- adrenaline
- noradrenaline
- dopamine
- serotonin
- (Neuro)peptides
- Acetylcholine
Name examples of inhibitory neurotransmitters.
- GABA
- Glycine
- Dopamine
Name examples of excitatory neurotransmitters.
- Acetylcholine
- Adrenaline
- Noradrenaline
- Dopamine
- Serotonin
- Glutamate
When are local chemical mediators used in signalling?
Local injury results in local signalling response - paracrine: rapid, focused and integrated.
Give examples of local chemical mediators.
- Cytokines (interleukins, chemokines, interferons, histamine)
- Eicosanoids (prostaglandins, leukotrienes)
- Others: nitric oxide, neuropeptides, platelet-activating factor
Give examples of therapeutic applications of pharmaceutical derivates of NTs.
- Propranolol antagonises adrenaline/noradrenaline: treatment of hypertension, thyrotoxicosis, etc.
- Dopamine precursors + agents to inhibit breakdown: treatment of parkinsonism
Give examples of therapeutic applications of pharmaceutical derivates of local chemical mediators.
- Inflammation: steroids are potent blockers of inflammatory signal of local mediators.
- Moderate pain: non-steroidal anti-inflammatories (NSAIDs) block local mediator pain signal.
What is endocrine signalling?
- Glands produce hormone signalling molecules - typically act over long distances/throughout whole body via bloodstream.
- Molecules are highly potent - picomolar to nanomolar range, with timescale of action ranging from seconds to months.
- Recipient cells need to express receptors.
Give examples of the therapeutic applications of exogenous endocrine analogues.
- Adrenaline i.v. Use in A&E
- Insulin derivates for blood sugar control in diabetes
- Steroid use as anti-inflammatories
- Steroids in contraception
What are the major types of hormones?
- Catecholamines
- adrenaline
- noradrenaline
- dopamine
- Peptides and proteins
- insulin
- atrial natriuretic peptide (ANP)
- oxytocin
- Steroids
- testosterone
- progesterone
What are catecholamine hormones, what is their mode of action and what is their plasma 1/2 life?
- Tyrosine derivatives
- Hydrophilic, receptors in PM
- Mode of action (msec-sec)
- Change in membrane potential
- Trigger synthesis of cytosolic second messengers
- Plasma 1/2 life = seconds
What are peptide/protein hormones, what is their mode of action and what is their plasma 1/2 life?
- Short to long chain of amino acids.
- Hydrophilic, receptors in PM
- Mode of action (min-hrs):
- Trigger synthesis of cytosolic 2nd messengers
- Trigger protein kinase activity
- Plasma 1/2 life = minutes
What are steroid hormones, what is their mode of action and what is their plasma 1/2 life?
- Derived from cholesterol lipid.
- Lipophilic, intracellular receptors (cytosolic or nuclear)
- Mode of action (hrs-days):
- Receptor-hormone complex controls transcription and stability of mRNA.
- Plasma 1/2 life = hours
What are the main types of drug targets, and what is the main exception?
- RITE: ~ Receptors ~ Ion channels ~ Transporters ~ Enzymes - In chemotherapy/antibiotics, drug target is often a structural protein or DNA.
What are the different types of receptors targeted by signalling molecules?
- KING: ~ Kinase-linked ~ Ion channels (ligand-gated) - ionotropic Rs ~ Nuclear/intracellular ~ G-protein coupled - metabotropic Rs
What is the MOA of kinase-linked receptors and give examples?
- Act via protein phosphorylation - causes signalling cascade of molecular switches - regulation of gene transcription.
- Takes hours.
- Mediate signals from a wide variety of protein molecules.
- E.g. Cytokinesis receptors
What is the MOA of ionotropic receptors and give examples?
- Ligand (e.g. ACh) binding causes ion channel protein to open, allows transmembrane movement of ions - ion currents and voltage change modulates AP generation in neurones and contraction in muscles.
- Coupled to Ca2+ signalling.
- Acts in milliseconds.
- E.g. Nicotinic ACh R.
What is the MOA of nuclear/intracellular receptors and give examples?
- Lipid-soluble ligand (steroids, thyroid hormone, vitD) binds to intracellular receptor and complex migrates to nucleus - binds to a gene TF - activates/inactivates gene(s).
- Takes hours.
- E.g. Oestrogen R.
What is the MOA of metabotropic receptors and give examples?
- 3 major types: Gs, Gi, Gq - activate different intracellular signalling routes via 2nd messengers, e.g. Ca2+ release, protein phosphorylation. Or allow ion channel to open - change in excitability.
- Act in seconds.
- E.g. Muscarinic ACh R.
