Cellular communication 2 Flashcards
Eicosanoids are derived from
polyunsaturated fatty acids
The main precursor to eicosanoids is
arachidonic acid
Eicosanoids have primarily __________ & _____________actions
autocrine & paracrine actions
Unlike steroids, eicosanoids usually bind to
cell surface receptors
Eicosanoids are ___________ in the producing cells
Not stored
Miscellaneous lipophilic chemical messengers bind to
cytoplasmic or nuclear receptors
Examples of peptide and protein chemical messengers include
posterior pituitary- vasopressin, oxytocin
anterior pituitary- FSH, TSH, GH, LH
Kidneys- renin, erythropoietin
etc.
Peptide and protein chemical messengers are generally
polar (hydrophilic) molecules
Peptide and protein chemical messengers do not
readily cross plasma membranes- usually bind to cell surface receptors
Peptide and protein chemical messengers circulate in
the bloodstream as unbound molecules
The subclasses within other chemical messengers include
nucleotides and nucleosides: adenosine & ATP
gases: nitric oxide, carbon monoxide
endocannabinoids: anandamide, 2-arachidonylglycerol
Adenosine and ATP are
purines
Nucleotides and nucleosides are not stored
in vesicles
CO and NO are
lipid-soluble molecules with paracrine actions
NO is synthesized from the
amino acid L-arginine
Both CO & NO serve as
retrograde neurotransmitters
Endocannabinoids are derived from
arachidonic acide
Endocannabinoids bind to _____________ receptors
CB-1 (CNS) and CB-2 (peripheral)
Endocannabinoids are _________________ but, they bind to
liphophilic; cell-surface receptors
Which categories of signaling molecules are stored in vesicles in the cell that synthesized the molecules?
small hydrophilic chemical messengers
peptide and protein chemical messengers
Which lipophilic chemical messengers are not derived from cholesterol?
eicosanoids
retinoids
endocannabinoids
Dopamine, Epi, NE, and the iodohtyronines are derived from which amino acid?
tyrosine
How many times does a G protein-coupled receptor span the plasma membrane?
7 times
______________ represent the largest and most diverse family of receptors on the cell surface
G protein-coupled receptors
G protein-coupled receptors are important in anesthesia b/c
1/2 to 2/3rds of all drugs target them
A diverse array of signaling chemicals that bind to GPCRs include
neurotransmitters
hormones
vasoactive peptides
odorants
tastants
local chemical factors
G proteins are molecular
switches and can inactivate themselves through inherent GTPase activity in the alpha subuint
What are the four G protein families?
Gs (“s” is for stimulatory)
Gi (“i” is for inhibitory)
Gq (no specific meaning for “q”)
G12, 13
What is the overall sequence of signal transduction through G protein-coupled receptors?
First messenger (ligand)–> GPCR–> effector–> second messenger–> cellular response
What are the three essential components that signal transduction through GPCRs?
a plasma membrane receptor with 7 transmembrane segments
G protein activates the effector enzyme or pathway
an effector generates an intracellular second messenger
G proteins are turned ON when
a ligand binds to the receptor-binding site
G proteins are turned OFF by
the intrinsic GTPase activity in the alpha subunit
GDP is bound to the
alpha subunit of the GPCR
The GPCR conformational change facilitates the release of
bound GDP and simultaneous binding of GTP to the alpha subunit
The first messenger signal at the G protein coupled receptor is terminated by:
diffusion of the ligand away from the receptor
chemical modification of the receptor to desensitize the receptor
The Gs alpha-s subunit stimulates
adenylyl cyclase
Gi (inhibits adenylyl cyclase)
Gq stimulates
phospholipase C
G12,13 activates
small G proteins
Cholera toxin chemically alters the
Gs subunit to inhibit the intrinsic GTPase activity
ends up stimulating the export of fluid across the interstitial epithelium
Pertussis toxin chemically alters the
Gi0 subunits,
leads to accumulation of cAMP
McCune-Albright syndrome is characterized by
defects of hormonal regulation
The McCune-Albright syndrome is caused by a
gain-of-function mutation of Gs that correlates with disturbance of Gs-controlled hormone production
Pseudohypoparathyroidism is caused by a
loss-of-function mutation of Gs
The effects of pseudohypoparathyroidism leads to
premature puberty with obesity, growth retardation, and skeletal deformities
Major effectors targets of Ga subunits include:
adenylate cyclases
phospholipase C
phospholipase A2
Major effector targets of GBy subunits include:
Gi0-regulated potassium channels
voltage-gated calcium channels
B-adrenergic receptor kinase (BARK)
