cell communication Flashcards
most common control system (feedback loop) for maintaining homeostasis
negative feedback loop
example of endocrine cell signaling
adrenal medulla releases epinephrine that binds to B1 receptors on heart
example of autocrine cell signaling
NE binding to presynaptic A2 receptor on save nerve terminal that released NE.
neurotransmitter signaling is a specific type of which form of cellular communication?
paracrine signaling
example of a receptor that performs compartmentalization
ryanodine receptor (Ryr) is a scaffolding protein. multiple components of signaling pathways come together on scaffolding proteins to increase their concentrations and effects
calcium channels do this as well
general flow through GPCR
first messenger (ligand) –> receptor –> effector –> second messenger –> cellular response
name 3 chemical messengers derived from arachidonic acid (these are all lipophilic)
prostaglandins
leukotrienes
thromboxanes (eicosanoids. ex: anandamide)
chemical messengers derived from tyrosine (4)
dopamine
NE
epi
iodothyronines
characteristics of steroid chemical messengers
derived from:
where they bind on target cells:
storage:
how they circulate in the blood:
derived from cholesterol
circulate in blood bound to a protein
bind to receptors in cytoplasm or nucleus of target cells
not stored in producing cells
characteristics of eicosanoid chemical messengers
derived from
primarily what kind of actions
how they bind to the cell
storage
precursor
derived from polyunsaturated fatty acids
arachidonic acid is main precursor
primarily autocrine and paracrine actions
unlike steroids, they usually bind to cell surface receptors
not stored in producing cells
which category of signaling molecules are stored in vesicles in the cells that synthesize the molecule (2)
hydrophilic messengers
peptide and protein messengers
opioid peptides include (6)
beta endorphins
dynorphins
enkephalins
substance P
calcitonin gene related peptide (CGRP)
orexins
hydrophilic chemical messengers include (4)
amino acids (glycine, glutamate, gaba, aspartate)
biogenic amines (DA, NE, epi, serotonin, histamine)
choline esters (Ach)
iodothyroxines (T4, T3)
lipophilic chemical messengers include (4, 2 have examples)
steroids (aldosterone, cortisol, testosterone, progesterone, estrogens)
eicosanoids (prostaglandins, leukotrienes, thromboxanes)
VitD, retinoids
how to G proteins turn off
GTPase activity in alpha subunit. catalyzes hydrolysis of GTP to GDP and Pi.
alpha subunit dissociates with effector and goes back to by subunit
what is bound to the alpha subunit of a GPCR when its in the off/inactive state
GDP
what is bound to the alpha subunit of a GPCR when a ligand has attached to the GPCR and it is turned “on” or in the active state
GTP
in the GPCR, what does the GDP GTP exchange do to the aby complex (after activation)
aby complex disassembles into GTP bound alpha subunit and separate by complex
in the activated GPCR, the alpha GTP subunit will interact with effectors that include either
adenylate cyclases (AC)
phospholipase C (PLC)
phospholipase A2 (PLA2)
in the activated GPCR, the by complex subunit will interact with effectors that include either
Gi-0 regulated potassium channels (GIRK)
VgCa2+ channels
B adrenergic receptor kinase (BARK)
heterotrimeric G proteins are classified into 4 families based on nature of alpha subunit (and what they stimulate/inhibit)
Gs (stimulates adenylate cyclase)
Gi, 0 (inhibits adenylate cyclase)
Gq, 11 (activates PLC)
G12, 13 (activates small G proteins)
activated GPCR alpha subunits target these 3 big down stream effectors (and know their second messengers)
adenylyl cyclase (AC) –> cyclic adenosine monophosphatate (cAMP)
phospholipase C (PLC) –> inositol triphosphate (IT3) and diacylglycerol (DAG)
phospholipase A2 (PLC2) –> eicosanoids (20 carbon lipid mediators)
adenylyl cyclase function, inbhibition and stimulation
AC converts ATP to cAMP
Gs stimulates cAMP while Gi inhibits cAMP
PLC function and stimulation
PLC converts PIP2 to IP3 and DAG (both second messengers)
Gq11 with Ca2+ activates PLC
function of IP3
soluble, diffuses into cytoplasm, binds to Ca2+ channels on ER. Ca2+ then is released into cytoplasm from ER
function of DAG
acts as docking site for activator PKC
function of increased cAMP in:
cardiac myocyte
AW and vessel smooth muscle
platelets
principal cell of nephron
cardiac myocyte: increased cAMP increases contractility via b1 receptors
AW and vessel smooth muscle: b2- increased cAMP causes relaxation and dilation
platelets: increased cAMP decreases aggregation (adenosine, P1A2 receptor)
principal cell of nephron: v2- increased cAMP promotes insertion of aquaporin 2 channels in apical membrane
how is the action of cAMP terminated
phosphodiasterases
how is the action of DAG terminated
when the molecule is recycled into new phospholipids
how is the action of IP3 terminated
when the molecule is recycled into new phospholipids
why is free Ca2+ a second messenger
because its an intracellular messenger
which two calcium transporters are found in the plasma membrane
sodium calcium exchanger (NCX)
Ca2+ ATPase (Pump, PMCA)
two types of human synapses in the body
chemical and electrical
Ach synthesis (6 steps)
- glucose enters nerve terminal by passive transport (facilitated diffusion)
- glycolysis converts glucose to pyruvate
- pyruvate is transported into mitochondrion. acetyl group from pyruvate is added to coenzyme A tp produce acetyl co-A which is transported back into the cytoplasm
- choline is actively transported into presynaptic terminal. choline is rate limiting step in Ach synthesis
- choline acetyltransferase (CHAT) catalayzes formation of Ach from acetyl CoA and choline
- Ach is transported into vesicles by H+ anti porter. ach is stored in synaptic vesicles until release
explain Ach elimination
acetylcholinesterase (AchE) in the synaptic cleft hydrolyzes Ach to acetate and choline. choline re enters the nerve terminal and is re used for Ach synthesis
what is required to initiate conformational change for nAchR’s
binding of two Ach’s to the alpha subunits
where are MAchR’s found (4)
CNS, heart, smooth muscle, glands of Gi tract
Gq MAchR’s include
M1, M3, M5
(all have same second messenger pathway)
Gi MAchR’s include
M2, M4
Receptor: NmAchR’s
Signal Transduction:
Locations:
Responses:
Signal Transduction: opening of nonselective cation channels, influx of Na
Locations: skeletal muscle at NMJ
Responses: end plate depol and skeletal muscle contraction
Receptor: NnAchR’s
Signal Transduction:
Locations: (3)
Responses: (5)
Signal Transduction: opening of nonselective cation channels, influx of Na
Locations: autonomic ganglia, adrenal medulla, CNS
Responses: depol of postsynaptic postganglionic neuron, secretion of catecholamines, arousal, attention, analgesia
Receptor: M1
Signal Transduction:
Locations: (2)
Responses: (4)
Signal Transduction: Gq11 –> PLC –> IP3 –> increase in DAG –> increase in Ca2+ –> increase in PKC
Locations: autonomic ganglia, CNS
Responses: excitatory response, arousal, attention, analgesia
Receptor: M2
Signal Transduction:
Locations: (2 specific)
Responses: (3)
Signal Transduction: by subunit of Gi–> increase in K (GIRK) opening
Locations: heart: nodal tissue and cardiac muscle
Responses: slowed spontaneous depolarization (decreased chronotropy, inotropy, dromotropy)
Receptor: M3
Signal Transduction:
Locations: (2)
Responses: (2)
Signal Transduction: Gq11 –> PLC –> increase in IP3 –> increase in DAG –>increase in Ca2+ and PKC
Locations: smooth muscle and Gi
Responses: contraction and increase in salivary secretions
Receptor: M4
Signal Transduction:
Locations: (1)
Responses: (1)
Signal Transduction: Gi, 0 –> inhibits AC –>decrease in cAMP –>
By subunit of Gi–> increase in GIRK (K channel) opening
Locations: CNS
Responses: negative feedback to decrease Ach release
Receptor: M5
Signal Transduction:
Locations: (1)
Responses: (2)
Signal Transduction: Gq11 –> PLC –> IP3 –>increase in DAG –>Ca2+ –> and PKC
Locations: CNS
Responses: promotes dopamine release, dilation of cerebral arteries
primary excitatory neurotransmitter in the brain
glutamate
primary inhibitory neurotransmitter in the brain
GABA