Exam 2 10/18 Britton Flashcards
Homeostasis definition
ability to maintain a constant internal environment within a living organism in response to changes
(temp, nutrition, stress, disease)
Maintaining homeostasis requires:
communication between neighboring cells/between cells and tissues in distant parts of the body
The body coordinates its functions by what types of cellular communication?
- neural
- endocrine
Neural signaling
chemical signaling via release of neurotransmitters between neurons and target cells
Endocrine signaling
chemical signaling through release of hormones into the bloodstream to elicit a response in target cells
Types of cell signaling molecules
- neurotransmitters
- hormones
- local mediators
Chemicals released from nerve terminals are called:
Neurotransmitters
Neurotransmitters combine with specific ____ on target cells
receptors
Hormones are secreted by ____ into ____
specialized endocrine cells; bloodstream
____ travel throughout the body to distant regions, where they elicit a response in target cells
Hormones
Chemicals that act locally on cells in their immediate environment are called:
Local mediators
_____ do not enter the blood and are not distributed throughout the body
Local mediators
Local mediators are ____ that are rapidly ____
peptides; destroyed or removed
Examples of cell signaling molecules
- growth factors
- cytokines
- prostaglandins
- histamine
Which signaling molecules are extracellular?
- neurotransmitters
- hormones
- local mediators
1st messengers
What is the main difference in modes of signaling?
The distance the signal travels to reach the target cell
Modes of chemical signaling (4)
- autocrine
- paracrine
- endocrine
- direct cell contact via gap junctions
Which cell signaling molecule(s) are involved in autocrine signaling?
Local mediators (growth factors, cytokines)
Which cell signaling molecule(s) are involved in paracrine signaling?
- local mediators
- neurotransmitters
Which cell signaling molecule(s) are involved in endocrine signaling?
Hormones
A molecule (like a protein) that has an affinity for a specific ligand is called:
Receptor
True or false: not all receptors have a binding specificity for a ligand that is coupled to a process that will evoke a response
False - all do
A signaling molecule that binds to a receptor is called:
Ligand
Where can receptors be located?
- cell surface
- inside the cell
The ligands for intracellular receptors are ____
hydrophobic
____ easily diffuse across cell membranes, where they bind with ____
Lipid-soluble molecules; intracellular receptors
Examples of hydrophobic signaling molecules
- steroid hormones
- vitamin D
- retinoic acid
What happens when ligand binds to intracellular receptor?
A complex forms
many complexes can function as transcription factors
The ligands for cell surface receptors are _____
hydrophilic
Examples of ligands for cell surface receptors
- neurotransmitters
- peptide hormones
- local mediators
____ cannot penetrate the lipid bilayer so their signaling mechanism is mediated by
Hydrophilic molecules; binding to cell membrane receptors
Main types of cell surface receptors (3)
- ion channel linked receptors
- G-protein coupled receptors
- Enzyme linked receptors
Signaling ligands for ion channel linked receptors
Often neurotransmitters
Ion channel linked receptors contain:
- Ion channel
- open or closed state is gated by the binding of a ligand to the receptors
What happens when neurotransmitter binds to ion channel linked receptor?
Ion channel pore opens and allows ions to flow across the membrane
Ion channel stays open until neurotransmitter dissociates
Ion channel linked receptors also known as:
- ligand-gated ion channels
- ionotrophic receptors
Examples of ion channel linked receptors
- nicotinic receptors
- N-methyl D-aspartate (NMDA) receptors
- GABA receptors
Steps of ion flow via ion channel linked receptor
- NT binds
- Channel opens
- Ions flow across membrane (extra to intracellular)
nAChR
Nicotinic receptor
Nicotinic receptor is composed of what subunits, and how are they arranged in the cell membrane?
- 2 alpha
- 1 beta
- 1 gamma
- 1 delta
Subunits assemble to form a pore in the cell membrane
Nicotinic receptor ligand
Acetylcholine (ACh)
Steps of nicotinic receptor activation
- 2 Ach molecules bind to 2 alpha subunits
- ion channel pore opens
- Na+ moves intracellularly
- K+ exit the cell
Nicotinic receptor activation causes _____ event
Depolarization
(excitation)
Where are nicotinic receptors located?
- neuromuscular junction
- autonomic nerve ganglia
- CNS
- adrenal medulla
Nico lives in NACA
Nicotinic receptor is an example of what type of receptor?
Ion channel linked receptors
GPCR is a ____ receptor with ____ transmembrane segments that are associated with ____
membrane; 7; G proteins
G proteins associated with GPCRs are ____
Heterotrimeric (have 3 different subunits)
G proteins have what subunits?
- alpha
- beta
- gamma
GPCR is also known as:
- G protein-linked receptors
- Trimeric G-protein-coupled receptors
- Metabotropic receptors
What is the largest family of cell surface receptors?
GPCR
GPCR mediate a response to a wide range of signaling molecules (ligands), including:
- hormones
- neurotransmitters
- peptides
- odorants
- tastants
GPCR associate with the ligand on what side?
Extracellular
Muscarinic receptors, alpha and beta adrenergic receptors, dopamine receptors are examples of:
GPCR
MAD
G proteins switch between ____ and ____ states
inactive GDP-bound; active GTP-bound
GPCR is associated with what energy source?
GTP
Explain the G protein signaling cycle
- ligand binds to the GPCR extracellular region –> induces conformational change of G protein
- GDP bound to alpha subunit is exchanged for GTP
- When GTP is bound, the alpha and beta-gamma dissociate
- GTP-bound alpha subunit and beta-gamma subunit can trigger cell response
- When GTP is hydrolyzed to GDP, complex resets/reassociates and signaling is terminated
When ligand binds to GPCR, G protein can activate several:
downstream pathways and effectors
GPCR mechanism of action can involve what enzymes/proteins/messengers?
- activation of effector enzymes that produce intracellular 2nd messengers (cAMP, IP3-DAG)
- activation of 2nd messengers (Protein kinase A) that trigger signaling cascades/stimulate gene transcription in the nucleus
- can directly activate nearby ion channels
GPCR’s are MAD; this is my CASA now!
What are 2nd messengers?
Intracellular signaling molecules released by the cell in response to exposure to extracellular signaling molecules
Receptors transduce ___ into ____ so that the extracellular signal may be propagated ____
1st messengers; 2nd messengers; intracellularly
Examples of 2nd messenger molecules
- cAMP
- cGMP
- inositol triphosphate (IP3)
- diacylglycerol (DAG)
- Ca2+
CCC my ID!!
To amplify the strength of the original 1st messenger signal, 2nd messengers may be coupled to:
Multi kinase cascade pathways (Ras/Raf/MAP)
G proteins can have a different set of ____ and is often categorized by the type of ___ present
subunits (alpha, beta, gamma); alpha subunit
Norepinephrine binds to ____ (type of GPCR) and causes activation of ___ (G protein type) to cause _____
beta-adrenergic; Gs; increase of protein phosphorylation
Glutamate binds to ____ (type of GPCR) and causes activation of ___ (G protein type) to cause _____
mGluR; Gq; increase in protein phosphorylation and activate calcium-binding proteins
Dopamine binds to ____ (type of GPCR) and causes activation of ___ (G protein type) to cause _____
Dopamine D2; Gi; decrease in protein phosphorylation
Muscarinic receptor is a type of:
GPCR
There are ___ receptor subclasses of muscarinic receptors
5
What is the ligand for a muscarinic receptor?
Acetylcholine (binds to M1, M2, M3)
Muscarinic receptors (and its ligand Ach) allow for mediation of:
Parasympathetic nerve control in different tissues and organs
“Inside muscles” = parasympathetic
True or false: Ach has inhibitory effects in all tissues it acts in
False - can have excitatory or inhibitory effects in specific tissues
The pathways activated by a particular GPCR are determined by:
The specific G-protein (Gs, Gq, Gi) associated with it
Which muscarinic receptor subclass is associated with gastric and saliva secretion?
M1 and M3
M3 is also vasoconstriction and eye accomodation
Which muscarinic receptor subclass is associated with slowing heart rate?
M2
Which G protein is associated with M1?
Gq
Which G protein is associated with M2?
Gi
Which G protein is associated with M3?
Gq
Enzyme-linked receptors have what kind of functions?
- enzymatic (catalytic)
- receptor
2nd biggest group of cell surface receptors
Enzyme-linked receptors
Enzyme-linked receptors have roles in:
- cell growth
- cell division/proliferation/differentiation
- apoptosis
- tissue repair
Enzyme-linked receptors structure
3 domains - ligand-binding domain, transmembrane domain, intracellular domain (enzymatic/active)
Ligands for enzyme-linked receptors
growth factors and cytokines, such as:
- EGF
- platelet-derived growth factor (PDGF)
- fibroblast growth factor (FGF)
The transmembrane domain is composed of a series of ____ amino acids in enzyme-linked receptors
Hydrophobic
Each subunit of enzyme-linked receptors has ___ transmembrane segment
1
The enzymatic portion of the enzyme-linked receptor is located on
Intracellular surface
Receptor tyrosine kinases are a type of
Enzyme-linked receptors
Mechanism of action of enzyme-linked receptors
- ligand (growth factor/hormone) binds to the receptor on the extracellular domain
- conformational change to transmembrane protein
- intrinsic enzymatic activity occurs
- leads to 2nd messengers and intracellular signaling cascades
Responses to ligands in enzyme-linked receptors are usually ____ and require ____
slow; many intracellular signaling steps
Signaling molecules released by neurons
Neurotransmitters
____ in neurons causes the release of neurotransmitter
Electrical signal
Neurotransmitters bind to receptor proteins on the target cell, which can be:
- neuron
- muscle
- gland
Neurotransmitters are hydrophobic or hydrophilic? Where do they bind?
Hydrophilic, so they can bind to cell surface receptors
True or false: each neurotransmitter ligand binds to several families of receptors
False - specific family of receptors (either ion channel-linked or GPCRs)
Primary chemical signals in the ANS
- Ach
- NE
_____ of neurotransmitters function in the CNS
Wide variety
Examples of neurotransmitters
- Norepinephrine (NE)
- Epinephrine
- Dopamine
- Acetylcholine
- Serotonin (5-HT)
- Histamine
- Glutamate
- GABA
- Opioids (endorphin, enkephalin)
“Neda’s Hogg”
- Neuropeptides are synthesized via ____ in the ___ of the nerve cell body and packaged into ____. Then transported to the nerve terminal by ______
OR - Neurotransmitters (amino acid derived) are synthesized and packaged into ____ in _____
- transcription and translation; ER; secretory granules; fast axonal transport
- synaptic vesicles; pre-synaptic nerve terminals
Ach synthesis occurs in the:
Presynaptic nerve terminal
Ach is synthesized from ____ through a reaction catalyzed by _____
Acetyl coenzyme A and choline; choline acetyltransferase
ACh is degraded by:
Acetylcholinesterase (AChE)
Catecholamines examples
- dopamine
- DOPA
- Norepinephrine
- Epinephrine
associated with fight or flight and you want it to ENDD
Catecholamines are all derived from:
Tyrosine
Tyrosine comes from
Diet
Catecholamine synthesis starts with conversion of tyrosine to:
Tyrosine –> DOPA –> dopamine –> norepinephrine –> epinephrine
Catecholamines are produced, stored, and released from ____ and the ____
Nerve terminals (neurotransmitters); adrenal medulla (hormones)
Serotonin synthesis occurs in the
Presynaptic nerve terminal
Serotonin precursor amino acid is
Tryptophan
Where does neurotransmitter signaling work?
- CNS synapses
- Neuromuscular junction
- Autonomic nerves
Signaling events at the CNS synapse
- APs arrive at axon terminal
- Voltage gated Ca2+ channels open
- Ca2+ enters the cell
- Ca2+ signals to vesicles
- Vesicles move to the membrane
- Docked vesicles release neurotransmitter by exocytosis
- Neurotransmitter diffuses across the synaptic cleft and binds to receptors
____ is the major excitatory neurotransmitter in the CBS
Glutamate
Glutamate activates 2 types of receptors:
- ionotropic receptors
- GPCRs (metabotropic receptors)
Glutamate activates ionotropic receptors that have an ____ and generate ______
Name the subclasses
integral ion channel (cation permeable pore); excitatory post-synaptic potentials
AMPA subclass, N-methyl-D-aspartate (NMDA) subclass
Glutamate activate GPCRs which activate:
Second messenger cascades like GluR1-GluR8
What is the NMJ?
Synapse between a motor neuron of the somatic nervous system and a skeletal muscle fiber
Skeletal muscle excitation begins with ACh binding to _____ on the muscle cell to result in _____
nAChRs; muscle contraction
True or false: At the NMJ, the neurotransmitter is always acetylcholine
True
Autonomic nerves are divided into what 2 groups?
- Cholinergic
- Adrenergic
Cholinergic
Transmission of nerve impulses mediated by ACh
Adrenergic
Transmission of nerve impulses mediated by NE and E
All adrenergic receptors are:
GPCRs
Acetylcholine can bind to what type of receptors:
- nicotinic (ligand-gated ion channels, excitatory)
- Muscarinic (GPCRs, excitatory or inhibitory)
Example of the effect of a common neurotransmitter binding to different GPCRs
NE or E binds to a1 receptor to activate a Gs protein that activates _____, which catalyzes the conversion of PIP2 to ______. ___ triggers Ca2+ release, and ____ activates protein kinase C
phospholipase C; IP3 and DAG; IP3; DAG
Predominant receptor in vascular smooth muscle; net effect is?
a1 adrenergic; arteriolar smooth muscle contraction
NE signaling at a2 adrenergic receptors
NE/E binding to a a2 receptor (GPCR) activates a Gi protein that decreases _____ activity and decreases ____. Net effect is _____
adenylate cyclase; cAMP; inhibitory
NE signaling at B1 adrenergic receptors
NE/E binding to B1 receptor (GPCR) activates a Gs protein to increase ____ activity and increase ____. Net effect is ____
adenylate cyclase activity; cAMP
increased heart rate and contractility
____ is the predominant adrenergic receptor in the heart
B1
The endocrine system consists of:
cells, tissues, organs that secrete hormones
Examples of endocrine glands
- pituitary
- thyroid
- parathyroid
- pancreas
- adrenal glands
- gonads
3 basic types of hormones
- peptide hormones
- amino acid-derived hormones
- steroid hormones
Peptide hormones are synthesized by _____ and often undergo ____ in the ER
gene transcription/translation; post-translational processing in the ER
Active peptide hormone is released via:
Packaged into secretory vesicles and released by exocytosis
Peptide hormones are released in response to:
Stimuli (ex. high blood glucose levels)
Examples of peptide hormones
- insulin
- antidiuretic hormone
- oxytocin
- follicle-stimulating hormone
Amino acid derived hormones are synthesized from
Tyrosine or tryptophan
True or false: amino acid derived hormones are relatively large molecules
False - small
Where are amino-acid derived hormones stored?
In endocrine cells until needed
Examples of amino-acid derived hormones
- catecholamines (epinephrine and norepinephrine synthesized in adrenal medulla)
- thyroxine (T4, thyroid gland)
- melatonin (pineal gland)
Steroid hormones are derived from
modification of cholesterol in the adrenal cortex, gonads, placenta
Steroid hormones are synthesized in
mitochondria and smooth ER
Steroid hormones examples
- cortisol
- aldosterone
- estrogen
- testosterone
- progesterone
Which hormones are water-soluble?
Amino acid derived, peptide hormones
What kinds of receptors are used for water soluble hormones?
- ion channel linked
- enzyme-linked
- G protein linked
all of the cell membrane receptors
Water-soluble hormone receptors will be located:
on cell surface (cannot pass through lipid membrane)
Steroid hormones are ____ soluble and thus can diffuse ____
lipid; into a cell membrane and nucleus
Where are steroid hormone receptors located?
Intracellular; or the hormone can control regions of gene to trigger gene expression
How are steroid hormones transported in blood?
They are water insoluble and need carrier proteins for transport in blood
Hormone binding transport proteins
Corticosteroid binding globulin
Albumin (non-specific)
Thyroxine-binding globulin
Sex hormone binding globulin
Which hormones do not need transport proteins to travel?
Amino-acid derived hormones, peptide hormones
True or false: steroids remain in circulation longer than peptide hormones
True
Cortisol half life
60-90 min
Epinephrine half life
1 min
Which of the following hormones does not require a binding protein for transport in blood?
A. testosterone
B. aldosterone
C. insulin
D. cortisol
C. Insulin
Tropic hormones
hormones that target other endocrine glands
Tropic hormones typically stimulate a gland to
release other/additional hormones
Most tropic hormones are released by:
Anterior pituitary gland
____ function in feedback loop systems
Tropic hormones
Regulation of hormone release can be done by:
- hormone regulation
- nutrient or ion regulation
- neural regulation
Examples of nutrient or ion regulation
- glucose stimulates insulin release from pancreatic beta cells
- oscillations of intracellular Ca2+ concentration in pancreatic beta cells
Examples of neural regulation of endocrine signaling
- stimulation of adrenal medulla by sympathetic nerves causes release of catecholamines (NE and E)
- circadian rhythms generate recurring cyclic release of hormones
- diurnal rhythms (cycle once a day) of gonadotropin and cortisol secretion