Exam 3: Receptor Systems and ANS Flashcards
What are the steps of signal transduction?
- Reception (Signal molecule and receptor binding)
- Transduction (Signal-transduction pathway)
- Response (Activation of cellular responses, secretion, smooth muscle metabolic hr, bp)
What are the properties of cell membrane receptors?
- Hydrophilic ligands can’t enter cell
- Binds to extracellular recpetors
- Fast responding
What are the properties of cytosolic or nuclear receptor binding?
- Lipophilic ligands diffuse through membrane into the cell to bind to receptors
- Activates or suppresses gene expression
- Slower responses depending on receptors
What is a G-coupled receptor?
A single proteins with seven transmembrane domains
What are the characteristics of G protein signaling?
- Trimeric protein that bind to quinine nucleotides
- Couple integral membrane receptors to target intracellular second messenger enzyme systems
- Molecular switch between inactive and active
- a subunit contains GTPases activity by hydrolyzes of GTP to GDP
Describe the resting state of G-protein signaling
G-a is associated with G-by and GDP
Describe the resting state of G-protein signaling
G-a is associated with G-by and GDP
Describe the activation of G-protein signaling
- GTP displaces GDP of a-subunit that dissociates from by subunits
- a stimulates adenylate cyclase that catalyzes cAMP from ATP
Describe the reassociation of G-protein signaling
- Intrinsic GTPase of a subunit hydrolyzes GTP to GDP
- a subunit returns to by subunits and induces resting state
Describe the signal transduction pathway induced by Gs?
- Drug binds to receptors activating G-proteins or protein kinases
- Gs is the transducer for adenylate cyclase
- Second messengers is cAMP from ATP and adenylate cyclase
- Second messengers increased Protein Kinase A (PKA)
- Ion channels open and increase intracellular Ca2+ activating other enzymes in the system (amplification of cellular responses)
How can increased intracellular cAMP increase gene transcription?
- Activated PKA enters the nucleus and phosphorylates CREB (cAMP response element binding)
- CREB recruits the coactivator CBP (CREB binding protein)
- CBP binds to CREB-binding element on DNA stimulating or inhibiting gene transcription
How can increased intracellular cAMP increase gene transcription?
- Activated PKA enters the nucleus and phosphorylates CREB (cAMP response element binding)
- CREB recruits the coactivator CBP (CREB binding protein)
- CBP binds to CREB-binding element on DNA stimulating or inhibiting gene transcription
How can increased intracellular cAMP increase gene transcription?
- Activated PKA enters the nucleus and phosphorylates CREB (cAMP response element binding)
- CREB recruits the coactivator CBP (CREB binding protein)
- CBP binds to CREB-binding element on DNA stimulating or inhibiting gene transcription
Describe the signal transduction pathway induced by Gi?
- First messenger binds to receptor
- Gi binds to adenylate cyclase inhibiting response
- Decreased cAMP production
- Decreased PKA
- Opening of K+ channels
Where are Gi regulations mainly found?
Muscarinic M2 receptors on heart
Adrenergic alpha-2 receptors are Gi
What is the G-protein link to Gq?
- Phospolipase C is activated by Gq hydrolyzed from PIP2
- PLC forms 2 second messengers
- DAG activates PKC
- PKC directly phosphorylates intracellular proteins and modulates gene expression through MAP kinase and NF-kb
- IP3 is activated to release Ca2+ from intracellular stores by binding to an IP3-gated Ca2+ channel in the ER
How can calcium be used as a second messenger system?
- Calcium binds to calcium binding protein such as calmodulin
- Ca2+/calmodulin complexes activate CaM-dependent kinases (CaM kinase II)
Why do we study autonomic pharmacology?
Determining the mechanism of drug action and anatomical information to predict the effects of drugs
What diseases are autonomic drugs used to treat?
- Angina
- Heart failure
- High BP
- Ocular pharmacotherapy
- ALzheimers
- GUT and prostatic hypertrophy
- Astma and COPD
- Septic and anaphylactic shock
What controls most autonomic function?
Pons and medulla
What is the purpose of the afferent (sensory) nervous system?
To maintain steady-state in an ever-changing environment
What are the 2 divisions of the ANS?
Para and sympathetic NS
What neurotransmitter activates the PNS?
ACh released by preganglionic (nicotinic) and postganglionic neurons (muscarinic)
What neurotransmitter activates the Sympathetic NS?
- ACh released by nicotinic receptors of preganglionic neurons
- Norepinephrine released by most postganglioninc neurons onto adrengegic receptors on end organs
Compare the lengths of pre and postganglionic neurons of the PNS and SNS?
PNS: long pre localized in ganglia, short post on innervated tissue
SNS: short pre localized in ganglion, long post
Describe the release of ACh in the adrenal medulla
- ACh is released onto nicotinic receptors by pressgang
- Nicotinic receptor is on adrenal medulla (modified catecholaminergic postganglionic secretory cell)
- Humoral release
What make sweat gland different from other SNS systems?
Release of ACh from both pre and postganglionic neurons
What are the cholinergic receptors?
- Nicotinic
- Muscarinic
What are the NE receptors?
Adrenergic
Where are ACh synapses found?
- All motor (skeletal) nerves
- All preganglionic autonomic nerves and adrenal medulla (nicotinic)
- All postganglionic parasympathetic nerves (muscarinic)
- Few postganglionc cholinergic sympathetic nerves (sweat glands, muscarinic)
Where are NE synapses found?
- Almost all postganglionic sympathetic fibers (adrenergic)
- Hormones release from adrenal medulla (NE and E bind to adrenergic)
What is the difference between cholinergic and noradrenergic in regards to rest and digest?
C: discharge promotes digestion and absorption of food
N: Discharge maintains arterial and venous tone
What is the NE and E response to fight or flight?
- Accelerates heat rate
- Increases BP
- Elevates plasma glucose
- Constricts blood vessels to skin and intestine
- Shuts of gastric secretion
- Lowers CNS threshold
- Relaxes pupils
What are the autonomic controls of the SA node?
Syp: increases heart rate at receptors a1, b1, b2
Par: Decreases heart rate at M2
What are the autonomic controls of the AV node?
S: Increases automaticity, conduction velocity at a1, b1, b2
P: Decreases automaticity, AV block at M2
What are the autonomic controls of the atrium?
S: Increases force and conduction velocity at a1, b1, b2
P: Decrease force and conduction velocity at M2
What is the autonomic controls of the ventricles?
S: Increases automaticity and contractile force at a1, b1, b2
P: Decrease automaticity and contractile force at M2
What are the autonomic controls of the arterioles?
S: Constriction at a1
P: Dilation (not innervated) at M3
What are the autonomic controls of skeletal muscles?
S: Dilation (Constriction) at b2 (a1)
P: Dilation (not innervated)
What are the autonomic controls of coronary?
S: Dilation (Constriction) at b2 (a1)
P: Dilation (not innervated)
What are the autonomic controls of veins?
S: Constriction at a1
What innervates the vasculature?
Sympathetic nerve fibers, there is no parasympathetic innervation of the vasculature
What are the autonomic controls of bronchial smooth muscle?
S: Relaxation, dilation (not innervated) at B2
P: Constriction at M3
What are the autonomic controls of bronchial glands?
S: Increased secretion (decreased secretion) at B2 (a1)
P: Increased secretion at M3
What are the autonomic controls of GIT smooth muscle?
S: Relaxation, decreased motility at a1, b2, presyn a2
P: Contraction, increased motility at M3
What are the autonomic controls of sphincters?
S: Contraction at a1
P: Relaxation at M3
What are the autonomic controls at glands and gastric acid?
S: Minimal effects
P: Secretion at M1
What nervous system division also control the GIT other than the autonomic?
Enteric NS
What are the autonomic controls of detrusor (bladder) muscle?
S: Relaxation at B2
P: Constriction at M3
What are the autonomic controls of trigone muscle (sphincter)?
S: Contraction at a1
P: Relaxation (minimal) M3
What are the autonomic controls of penis?
S: Ejacualation at a1
A: Erection at M
What are the autonomic controls of renin secretion?
S: Increase renin at B1
P: none
What are autonomic controls of the uterus when pregnant?
S: Contraction at a1
P: Variable at M3
What are autonomic controls of the uterus when not pregnant?
S: Relaxation at b2
P: Variable
What are autonomic controls of radial muscle of iris?
S: Contraction (mydriasis/dilation) at a1
P: None
What are autonomic controls of the sphincter muscle in the iris?
S: None
P: Contraction (miosis) at M3
What are the autonomic controls of ciliary muscle?
S: Relaxation (slight) at B2
P: Contraction (Near vision, accommodation) at M3
What are autonomic controls of lacrimation?
P: Increases at M3
What are the autonomic controls of ciliary epithelium?
S: Increases aqueous humor secretion at B2
What are the autonomic controls of thermoregulatory sweat glands?
Sympathetic cholinergic increases sweating at M3
What are the autonomic controls of apocrine glands?
S: Increases sweating in palms at a1
What are the autonomic controls of pilomotor?
S: Piloerection at a1
Wha are the autonomic controls of salivation?
S: Secretion of K+ and H20 at a1, secretion of amylase at b
P: Secretion of K+ and H20 at M3
What are the autonomic controls of liver?
S: Glycogenolysis and gluconeogenesis at a1 and b2
P: Glycogen synthesis at M
What are the autonomic controls of fat cells?
S: Lipolysis at B3
What are the autonomic controls of insulin secretion?
S: Decreases at a2
P: Increases at M
