The Biochemical Basis for Therapy: Receptors and Signalling Flashcards
What are receptors?
Sensing elements of chemical communication in the body - neurotransmitters, hormones or other mediators (eg chemokines and cytokines)
What is the key characteristic of receptors?
Ligand selectivity
What are the 3 types of signalling cells?
Autocrine, paracrine and endocrine
What is an autocrine cell?
A cell that signals itself
What is a paracrine cell?
A cell that signals its close neighbours
What is an endocrine cell?
A cell that signals via molecules transported by the blood to target cells (ie signal molecule is in the circulation)
What are the 4 major types of receptors?
Ligand gated ion channels (ionotropic), G-protein coupled receptors (metabotropic), kinase-linked receptors (enzyme-linked) and nuclear receptors
What is the location and targeting cells of LGICs?
At the plasma membrane and targeted by hydrophilic signalling molecules (eg fast neurotransmitters) - action of a millisecond timescale
What is the location and targeting cells of GPCRs?
At the plasma membrane and targeted by hydrophilic signalling molecules (eg slow neurotransmitters) signal on a second timescale
What is the location and targeting cells of kinase-linked receptors?
At the plasma membrane and targeted mainly by hydrophilic protein mediators, worked on an hours time scale
What is the location and targeting cells of nuclear receptors?
In nucleus (sometimes in cytoplasm) and targeted mainly by hydrophobic signalling molecules - very slow (hours/days)
What are some common hydrophilic signalling molecules?
Acetylcholine, amino acids, amines, peptides, adrenaline and peptide hormones
What are some common hydrophobic signalling molecules?
Steroid and thyroid hormones
Where does hydrophilic targeting occur?
Extracellularly, usually at the membrane
Where does hydrophobic targeting occur?
Intracellularly
What are ion channels?
Transmembrane pores formed by glycoproteins that span the membrane to create an ion conducting pathway for selected ions
What usually regulates ion channels?
Signals that cause the channel to cycle reversibly between a closed, non-conducting state and an open, conducting conformation = gating
What happens when ion channels are open?
Conduct selected ions (passively) down their electrochemical gradients quickly which often mediates very rapid electrical signals
What can gate an ion channel?
Chemical signals (eg LGICs), transmembrane voltage (VGICs) and physical stimuli (thermal and mechanical energy)
What are the 2 main examples of LGICs?
Nicotonic-acetylcholine receptor (of skeletal muscle) and neurones
What is the structure and function of LGICs?
Consists of separate glycoprotein subunits that form a central, ion conducting channel that allows very rapid changes in the permeability of the membrane to certain ions. Come rapidly after the membrane potential
What is the sequence of LGIC activation?
Agonist binds = conformational change. Channel opens = conduction pathway for certain ions. Ion flow down the electrochemical gradient
What are second messenger systems?
Where receptor activation modulates the activity of an effector, usually an enzyme (or ion channel). The receptors are GPCRs and are linked to effectors by G proteins. Enzyme effectors can increase or decrease the rate of synthesis of second messenger molecules = change in activity of their targets
What do ion channel effectors cause?
Changes in membrane electrical properties
