Transducer Mechanism Flashcards
Most transmembrane signaling is accomplished by a small number of different molecular mechanisms (transducer mechanisms).
Large number of receptors share these handful of transducer mechanisms to generate an integrated response.
Mainly 4 (four) major categories:
GPCR
Receptors with intrinsic ion channel
Enzyme linked receptors
Transcription factors (receptors for gene expression)
GPCR is a large family of cell membrane receptors linked to the effector enzyme/channel/carrier proteins through?
one or more GTP activated proteins (G-proteins i.e. guanine nucleotide binding protein)
GPCR Are cell surface receptors called?
seven-transmembrane domain receptors
And they Mediate the majority of cellular responses to external stimuli
All receptors have common pattern of structural organization
The molecule has _____ membrane spanning hydrophobic amino acid segments ____
7 α-helical
3 extra and 3 intracellular loops
The ligands that bind and activate these GPCR receptors include 4 things? And they vary in size from small molecules to peptides to large proteins.
light-sensitive compounds
odours
hormones
neurotransmitters,
The body consists of certain molecules (essentially proteins) that specialize in recognizing ___ ___and thereafter, translate them into ___ ___.
Chemical signals
Cellular responses
Ion-Channels: Are modulated through 2 different means
- ligand-gated (ionotropic receptors)
Ion-channels open/close when ligands bind to the receptor - voltage-gated: the rate and direction of ion movement through the pore is governed by the electrochemical gradient (as measured by its concentration on either side of the membrane as well as the membrane potential) for each ion.
Drug action is more complex than it is perceived t/f
True
Drug action is more complex than it is perceived? T/F
True
Transmembrane Ligand-gated ion channels (Ionotropic):
Similar in structure to other ion-channels but incorporates a_____ _____ ______
Responsible for the regulation of the flow of ions across cell membranes
ligand-binding site, which is found extracellularly.
Ionotropic Ligand-binding and channel opening occur on a millisecond timescale, so they are confined to _______
Eg?
excitable tissues-
CNS, NMJ, autonomic ganglia.
Receptors mediate diverse functions, including neurotransmission, cardiac conduction and muscle contraction
For example, stimulation of nicotinic receptor by ACh results in sodium influx,then?
generation of an action potential, and activation of contraction in skeletal muscle.
Also, Benzodiazepines, enhance stimulation of gamma-aminobutyric acid (GABA), resulting in increased chloride influx and.
hyperpolarization of the respective cell
G-protein coupled receptors Are membrane bound receptors which bound to effector system through _____ (______)
They do not have _______ but activate a _______ that in turn activates a _______that in turn will activate something else.
G-proteins (Metabotropic)
Channels
G-protein
secondary messenger,
G-proteins are ______ _____ molecules having 3 subunits ___ ___ & ___
Based on α-subunit, they are further classified into 3 main varieties ____ ____ _____
hetero trimeric
α, β and ϒ. (known as Gα, Gβ, and Gϒ, respectively).
Gs, Gi and Gq.
Gi
Gs
Gq
Inhibits adenylyl cyclase
Stimulates Adenylyl cyclase
Stimulates phospholipase C
Note: G12/13 regulate actin cytoskeletal remodeling in cells during during movement and migration, including cancer cell metastasis.
The consequence of GPCR depends on ______
Ligands include:
The type of G protein
adenosine, bradykinin, endothelin, opioid peptides, dopamine, serotonin, acetylcholine (muscarinic effects), histamine, chemokines, eicosanoids, adrenaline, noradrenaline etc.
The G proteins are rendered inactive when **reversibly bound to_________, but active when bound to _____________
Guanosine diphosphate (GDP)
Guanosine triphosphate (GTP).
The inactive G protein is bound to the receptor in its ______ state.
Once the receptor is recognized, the receptor changes in its _______ and therefore, mechanically activates the G protein, which does what?
The receptor can now _________ or _______
Inactive
Conformation
detaches from the receptor.
activate another G protein or switch back to its inactive state.
What happens upon activation of GPCR
Upon activation, the subunits of the G protein dissociate from the receptor, as well as from each other to yield Gα-GTP monomer and a tightly interacting Gβϒ dimer, which are now free to modulate the activity of other intracellular proteins.
List the gprotein, effector and substrate of GPCR
Gs: Adenylyl cyclase increase - Beta-receptors,
H2, D1 through cAMP
Gi: Adenylyl cyclase decrease - Muscarinic M2
D2, alpha-2 through cAMP
Gq: Phospholipase C increase - Alph-1, H1, M1,
M3 through IP3& DAG
Go: Ca++ channel decrease - K+ channel in heart, sm
