L14 Flashcards
AC is inhibited and stimulated via G protein
True
what subunit is different in G protein that stimulates AC
alpha s – stimulates AC
alpha i – inhibits AC
what receptors are coupled to Gs proteins
b-adrenoceptors
what receptors are coupled to Gi proteins
a2 adrenoceptors
how does the cholera toxin work
Signalling via G proteins depends upon exchange of GDP for GTP
Active a subunit has GTP bound
Hydrolysis of GTP leads to inactivation
Cholera toxin (CTx) acts on as subunit and causes ADP-ribosylation
This prevents hydrolysis of GTP
Causes persistent activation of a subunit
In colon causes activation of PKA-dependent Cl- channels and “secretory diarrhoea”
what is lost from the body in cholera
Na
Cl
water
how does Pertusiss toxin work
Pertussis toxin acts on ai subunits
In this case locks subunit into inactive configuration
Prevents activation by receptors
Prevents inhibitory control over AC / PKA
Again leading to increased levels of cAMP and PKA
In airway leads to symptoms of whooping cough
what are the features of Gq
G proteins containing aq11 subunits allow hormones / neurotransmitters to activate amplifier enzyme Phospholipase C (PLC)
Underlies autonomic effects of acetylcholine (eg salivary secretion, bronchial smooth muscle contraction)
Histamine H1 receptor responses (G.I. smooth muscle contraction, allergies etc.)
Responses due to increased internal Ca2+
ACh also activates Muscarinic receptor “metabotropic receptor”
true
muscarinic receptors dont bind nicotine
False
Muscarinic receptors are Gq/Gi coupled receptors
true
what muscarinic receptors are Gq coupled
1,3, and 5
what muscarinic receptors are Gi coupled
2 and 4
Gq proteins second messengers are products of phosphoinositide breakdown
True
how does Gq work
Gq proteins stimulate phospholipase C (PLC)
PLC cleaves PIP2,a membrane phospholipid, into inositol 1,4,5-triphosphate (IP3) and diacylglycerol (DAG)
IP3 is the water soluble part of PIP2 and travels through the cytosol to stimulate
Calcium release from ER
DAG remains in the membrane (hydrophobic part) where it recruits Protein Kinase C (PKC)
IP3 is a second messenger that stimulates Calcium release from ER
True
how does IP3 stimulates Calcium release from ER
Since IP3 is hydrophilic it enters the cytoplasm
Binds to receptors on ER and promotes release of stored Ca2+
Also promotes Ca2+ influx from extracellular fluid by a mechanism that is less clear
Resultant increase in intracellular free Ca2+ promotes cellular responses
what are the features of calcium mediated Intracellular responses
Mediated by Ca2+ -binding proteins
Calmodullin (CaM) is the most important
Each CaM binds 4 Ca2+ ions
Ca2+-CaM complex activates PDE (the enzyme that degrades cAMP)
Importantly, Ca2+-CaM complex activates
CaM kinases (CaMKs)
CaMKs phosphorylate Serine and Threonine residues on a number of substrate proteins
CaMKs are involved in smooth-muscle contraction.
α1 adreno-receptor is a Gq coupled protein receptor which mediates vascular smooth muscle contraction by increasing intracellular free Ca2+ activating CAMKs (vasoconstriction)
what are the effects of DAG
DAG is hydrophobic and so remains in the plasma membrane
Presence of DAG increases the activity of Ca2+-dependent protein kinase
Evokes cellular responses by phosphorylating other proteins. The most important one is proteins kinase C (PKC)
PKCs can potentiate the effects of IP3
Mediates desensitization (cf b-ARK)
Regulates cell shape, cell proliferation and transcription factor activity
PKC also activate proteins regulating cell shape, cell proliferation and transcription factors
what are the effects of a1-adrenoceptor
on blood pressure
It causes vascular smooth muscle tone contraction (‘vasoconstriction’)
via Gq-PLC-IP3-CaMK
Makes blood pressure to increase
what are the effects of beta 2-adrenoceptor
on blood pressure
Cause relaxation of vascular smooth muscle (‘vasodilation’)
via Gs-cAMP-PKA
Makes blood pressure to decrease
just adrenergic receptors can cause smooth muscle contraction
false
what are the features of H1 histamine receptor
A Gq protein coupled pathways important in Asthma as it causes smooth muscle contraction in the airways (broncospasm)
give 2 receptors that are linked to a Gi protein
alpha 2 adrenergic receptor
M2 muscarinic receptor