Lecture 4 Vasopressin Flashcards
Three physiological roles of vasopressin
Regulates water excretion by kidney
Potent vasoconstrictor
Serves as a releasing factor for ACTH
What is desmopressin
A vasopressin analogue
Where does vasopressin act
Smooth muscle and kidney
What does vasopressin do
Vasoconstriction in smooth muscle
Aquaporins and water retention in kidneys
How does vasopressin affect ACTH levels
It increases them
What kind of feedback to vasopressin comes from
A. Nausea, vomiting, stress, exercise
B. Caffeine alcohol
C. Increase in osmolarity, decrease in blood volume
Positive feedback
Negative
Positive
How does increase in plasma osmolarity affect AVP release
Activates third ventricle osmoreceptors
How does fall in blood volume affect AVP level
Activates baroreceptor in heart and aorta in response to a fall in blood volume (8% or larger)
What five things regulate AVP release
Plasma osmolarity increase Fall in blood volume Modulation by angiotensin II Modulation by estrogens Heat increases AVP secretion (preceding thirst)
How does 2 percent increase in ECF osmolarity affect CNS
It activates osmoreceptors
What do CNS osmoreceptors influence
+ feedback ADH release
+ feedback angiotensin II release
What does + ADH released
Positive feedback antidiuresis
Positive feedback water conservation
Positive feedback in circulating volume and decrease in ECF osmolarity
What does ten percent decrease in circulating volume cause
Neg feedback baroreceptors Neg feedback angiotensin II Neg feedback thirst Less water acquisition Less circulating volume More ECF osmolality
What tissue in nephron does ADH target
Distal convoluted tubule and collecting tubule
Three types of vasopressin receptors.
V1, V2, V3
V1 location and function
Blood vessels
Vasoconstriction
V2 location and function
Renal collecting duct epithelium
Increased water permeability
V3 location and function
Anterior pituitary gland
Stimulation of adrenocorticotropin release
V1a(AVPR1A) signaling mechanism, location and function
Inositol triphosphate generation and calcium mobilization
Blood vessels, kidney, liver, brain
Vasoconstriction, platelet aggregation, release of factor VIII and Von Willebrand factor
V1b (AVPR1B) signaling mechanism, location and function
Inositol triphosphate generation and calcium mobilization
Pituitary, brain
ACTH secretion, behaviors such as memory and social recognition
V2 (AVPR2) signaling mechanism, location and function
Adenylate Cyclase
Renal collecting duct epithelium
Increased water permeability secondary to insertion of aquaporin-2 channels in apical membrane of collecting duct epithelial cells
V1R or V1a is couple to
It activates what and results in what
Gq/11
Phospholipases C, D and A2
Stimulates phosphatidyl inositol and results in intracellular calcium concentration increase
Steps of adenylate Cyclase activation and formation of cAMP
Hormone bonds to receptor Conformational change in receptor Receptor binds to G alpha subunit G alpjpha suffers conf. Change GDP bound to G alpha is replaced by GTP Alpha dissociates from gamma and beta Alpha binds to adenylate Cyclase Activates camp synthesis Hormone dissociates Hydrolysis of GTP to GDP causes alpha to dissociate from adenylate Cyclase and bind to beta gamma
How does cAMP regulate via cAMP-dependent kinase
CAMP binds to cAPK
Releases C subunit, two of them
C subunit enters nucleus and phosphorylates transcription factors
How is aquaporin 2 inserted into plasma membrane of collecting ducts
cAMP induces AQP2- rich vesicles translocation to plasma membrane and stimulates transcription of AQP2 gene increasing levels of this water channel
How does vasopressin increase arterial pressure
Vasoconstriction
Increased blood volume
Diabetes insipidus
What is it
What could cause it
Inability of kidney to conserve water
Deficiency in AVP
AVP gene mutation or injury to pituitary
What kind if mutations of SVP 2
Dominant x-linked inheritance mutation in V2 receptor
Mutation in aquaporin 2
What can inappropriate SVP secretion cause
Water retention
What is aquaresis
Specific loss of water with minimal loss of ions for the treatment of patients with congestive heart failure
What blood clotting factors does ADH release
Factor VIII
Willebrand factor
What cognitive functions does ADH affect
Memory consolidation and retrieval
How does vasopressin affect voles and transgenic mice
It may make them sociable and monogamous. Affects pair bonding.
