DEN 7101: signaling molecules and receptors

neurotransmitters are chemicals released from ___________ and they can combine with specific receptors on target cells

nerve terminals

__________ are secreted by specialized endocrine cells into the bloodstream that can travel to distant regions

hormones

__________ are chemicals that act locally in their immediate environment and are not released into the blood

local mediators

true or false: local mediators are peptides that can be rapidly destroyed or removed

true

_______ signaling is signaling to oneself and is accomplished by _____________

autocrine, local mediators

____________ signaling is signaling to a nearby cell and can be accomplished through local mediators and ___________

neurotransmitters

__________ signaling is signaling to a distant cell through the blood stream and is accomplished by ___________

endocrine, hormones

a __________ is a molecule that has an affinity for a specific ligand

receptor

a _______ is a signaling molecule that binds to a receptor

ligand

examples of ligands

neurotransmitters, hormones, drugs, cytokines, antibodies

locations of receptors

1. intracellular

2. cell surface

the ligands for intracellular receptors are ______-soluble/_________

lipid, hydrophobic

lipid soluble ligands diffuse across ___________ and bind to intracellular receptors or can function as transcription factors that can bind DNA to regulate gene transcription

cell membranes

ligands that bind to cell surface receptors are __________

hydrophilic

three main types of cell surface receptors

1. ion channel linked receptors

2. G-protein coupled receptors

3. enzyme linked receptors

ion channel linked receptors contain an ion channel who can be ________ or ___________ depending on the binding of a ligand to the receptor

open, closed

signaling ligands of ion channel linked receptors are often ___________

neurotransmitters

examples of ion channel linked receptors

nicotinic receptors, NMDA receptors, GABA receptors

nicotinic receptors are composed of _____ subunits that function to bind __________ to allow Na+ to move intracellularly and K+ ions to flow out of the cell, which causes a depolarization event

5, acetylcholine (ACh)

g protein coupled receptors are ____________ (contain 3 distinct subunits) that response to a variety of ligands such as hormones, neurotransmitters, peptides, etc

heterotrimeric

examples of gpcrs

muscarinic receptors, alpha/beta adrenergic receptors, dopamine receptors

gpcr cycle through states in which the g protein is _________ GDP-bound and _________ GTP-bound

inactive, active

when the ligand binds the gpcr extracellular region, the g-protein goes through a conformational change and the GDP bound by the ________ subunit is exchanged for _________

alpha, GTP

when ______ binds to the alpha subunit, the alpha subunit dissociates from the beta complex

GTP

signaling is terminated when the GTP is ________ into GDP and the trimeric G protein reassociates

hydrolyzed

in gpcr, activation of _____________ produced intracellular 2nd messengers such as adenylate cyclase and phospholipase C

effector enzymes

activation of the 2nd messengers triggers signaling ________ or stimulates gene _________ in the nucleus

cascade, transcription

true or false: some activated g-proteins can directly activate nearby ion channels

true

importance of second messengers

propagate an extracellular signal intracellularly

examples of 2nd messengers

cyclic AMP, cyclic GMP, inositol triphosphate, diacylglycerol, calcium

true or false: 2nd messengers can be coupled to multi kinase cascade pathways to amplify strength of the original 1st messenger signal

true

g proteins can have a different set of alpha, beta, and _______, which increases the diversity of cellular signals

gamma

muscarinic receptors are an example of __________, and the ligand that binds them is _________

g-protein coupled receptors, acetylcholine

true or false: ACh can only have excitatory effects on tissues

false (different g proteins in each pathway allows for a diversity in effects of the signal)

enzyme linked receptors possess both _______ and receptor functions

enzymatic

the three parts of enzyme linked receptors are

ligand binding domain, transmembrane domain, enzymatic domain

the ligand binding domain is located on the _________ surface

extracellular

the transmembrane domain is composed of _________ amino acids that span the cell membrane

hydrophobic

the enzymatic domain is on the __________ surface and has intrinsic ________ activity

intracellular, enzyme

enzyme linked receptor mechanism of action

1. ligand binds extracellular domain

2. ligand binding causes a conformational change to the transmembrane protein (eg.dimerization)

3. intrinsic enzymatic activity occurs and an intracellular signaling cascade occurs

neurotransmitters are hydrophilic signals released by ______ that bind to cell surface receptors

neurons

_________ and ________ are the primary chemical signals in the ANS

acetylcholine, norepinephrine

there is a wide variety of neurotransmitters in the _____

CNS

common examples of neurotransmitters

norepinephrine, epinephrine, dopamine, acetylcholine, serotonin, histamine, glutamate, GABA, opioids

__________ are synthesized and translated in the ER and transported to the nerve terminal, while __________ are synthesized and packaged into synaptic vesicles in pre-synaptic nerve terminals

neuropeptides, neurotransmitters

acetylcholine synthesis occurs in the ______________ nerve terminal from _____________ and choline

presynaptic, acetyl CoA

acetylcholine is degraded by __________

acetylcholinesterase (AChE)

catecholamines are derived from __________

tyrosine

examples of catecholamines

dopamine, DOPA, norepinephrine, and epinephrine

NE and E released from the adrenal medulla are ________, not neurotransmitters (structurally the same molecules)

hormones

serotonin is synthesized in the _________ nerve terminal and it's precursor is __________

presynaptic, tryptophan

where does neurotransmitter signaling occur

1. CNS synapses

2. Neuromuscular junctions

3. Autonomic nerves

glutamate is a major excitatory neurotransmitter in the _____, that can bind ionotropic receptors and GPCRs

CNS

the neuromuscular junction is a synapse between somatic nerve motor neurons and __________ fibers

skeletal muscle

the neurotransmitter for the neuromuscular junctions is always _______ that bind to ________ receptors

acetylcholine, nicotinic

autonomic nerves are diverged into 2 groups

cholinergic and adrenergic

__________ nerves are mediated by ACh and ________ nerves are mediated by NE and E

cholinergic, adrenergic

NE/E signaling to alpha-1 receptors in the ANS activates ____________, which causes arteriolar smooth muscle _________

phospholipase C, contraction

NE/E signaling to alpha-2 receptors activates Gi proteins and _________ cAMP, therefore having an overall _______ effect

decreases, inhibitory

NE/E signaling to beta-1 receptors activates the Gs protein to ________ cAMP, leading to _________ heart rate and contractility

increase, increased

3 types of hormones

peptide, amino acid derived, steroid

__________ are synthesized by gene transcription and translation, which are often released in response to stimulus

peptide hormones

examples of peptide hormones

insulin, antidiuretic hormone, oxytocin, follicle-stimulating hormone

_________ are synthesized from tyrosine or tryptophan

amino acid derived hormones

examples of amino acid derived hormones

catecholamines, thyroxine, melatonin

__________ are derived from cholesterol in the adrenal cortex and synthesized in the mitochondria and __________ ER

steroid hormones, smooth

examples of steroid hormones

cortisol, aldosterone, estrogen, testosterone, progesterone

______ and ________ hormones are water soluble molecules and can not pass through the plasma membrane, therefore their receptors are found on the surface of target cells

amino acid derived, peptide

_______ hormones are lipid soluble and can diffuse into cell membrane/ nucleus

steroid

steroid hormones need ________ for transport in blood

carrier proteins

true or false: steroids can remain in the blood longer than peptide hormones because they have a longer half-life

true

practice question: which of the following hormones does not require a binding protein for transport in blood?

a. testosterone

b. aldosterone

c. insulin

d. cortisol

insulin (it is a peptide hormone, therefore it is water soluble)

_________ hormones regulate the release of hormones because they are able to stimulate glands to release other/additional hormones (feedback loop systems)

tropic

most tropic hormones are released by the _______________

anterior pituitary gland

___________ such as glucose and calcium ions can regulate the release of hormones

nutrients or ions

release of NE and E can be regulated neurally by ________ in the ANS

nerves

__________ in circadian rhythms and diurnal rhythms neurally regulate hormone release

master clocks