Vasopressin Flashcards
AVP structure
nonapeptide with 1 internal disulphide bridge
where is AVP produced
magnocellular cells (SON & PVN)
what does AVP do to blood vessels
vasopressor agent
contracts blood vessels (anti-diuretic hormone ADH)
how does AVP regulate plasma osmolarity
hyperosmotic plasma increases AVP to form concentrated urine
hypoosmotic plasma decreases AVP to form diluted urine
what is normosmotic plasma
280-295 mOsM
action of alcohol on AVP
inhibits AVP
forms hyperosmotic plasma
how are aquaporins inserted into the tubule cell membrane
AVP released from peritubular capillary binds to V2 R on basolateral membrane
AC
cAMP
PKA
aquaporin inserted into apical membrane
chemoreceptors monitoring blood
trigger AVP and thirst
organum vasculosum of the lamina terminalis - OVLT circumventricular (no BBB)
AVP release
AVP released from axons and dendrites
PHASIC bursting (burst of depolarisation)
increased frequency means increased stimulus
benefits of phasic activity
keep recruiting other AVP neurons to reduce hypoosmotic stimulus
allows prolonged AVP release
what does hypertonic saline cause
increases plasma AVP
can be reversed by drinking
what does failure of ADH activity cause
diabetes insipidus
head injury to pituitary stalk
Rat produces 20L of hypoosmotic urine a day
what does diabetes insipidus cause
thirst
polydipsia
hypovolemia
decreased bp
tachycardia
decreased bp in atrium, aortic arch, carotid sinus
AVP released
acts on V1 a R on vascular smooth muscle
AVP vs OT firing patterns
OT - bursting synchronised - spike release
AVP - phasic recruitment - maintained release
pair bonding in male and female prairie voles
females - AVP has no effect
males - AVP induces pair bonding acts on V1a R (high density in ventral forebrain)
Gobrogge and Wang (2015) V1a R overexpression in meadow voles
increases time spent huddling
old field mice vs deer mice
monogamous old field mice - mimic female parental care
polygamous deer mice - little/absent parental care
AVP mRNA expression in deer mice
highly expressed in hypothalamus
high CNS AVP prevents parental care
Bendesky et al., 2017
administer ICV AVP in old-field mice inhibits nest building
super-region for maternal behaviours
MPOA & BNST (bed nucleus of the stria terminalis)
AVP release in the amygdala vs PVN
central amygdala - aggressive behaviour
PVN - unaffected
(Bosch et al., 2010) inject AVP-ant into MPOA/BNST
decreased maternal aggression
decreased no of attacks
decreased frequency of attacks
increases latency before attack
AVP and OCD
CSF AVP correlates to OCD in children
increased V1a R expression in PVN of depressed patients
V1 a R KO causes less anxious behaviour
ASD symptoms
deficits in social communication, interaction and repetitive behaviour
(Parker et al., 2019)
phase II VANILLA trials
Balovaptan (V1a R antagonist)
significant improvement of ASD at high doses
