Vasopressin and Oxytocin

Which hypothalamic nuclei make vasopressin and oxytocin?

paraventricular and supraoptic

What type of neurons make vasopressin and oxytocin?

magnocellular neurons

What are the two parts of the paraventricular nucleus?

magnocellular and parvocellular

What is the difference between the magnocellular and parvocellular parts of the paraventricular nucleus?

magnocellular - axons to post. pituitary for release

parvocellular - doesn’t release to post. pituitary, central neural actions and connections to ANSand regulates hormonal responses.

What are the steps in vasopressin processing?

prepro-vasopressin → pro-vasopressin → vasopressin + neurophysin II + glycoprotein (copeptin)

What substance can be measured as a proxy of vasopressin synthesis?

copeptin

What are the 3 vasopressin receptor types?

V1aR, V1bR (V3), V2R

Where are V1aR receptors located in the periphery?

vascular smooth muscle cells, platelets, liverW

Where are V1aR receptors located in the CNS?

hippocampus, hypothalamus, basal ganglia, limbic system, olfactory bulb, choroid plexus, astrocytes

What signalling pathway do V1aR receptors use?

G-protein → PLC → IP₃ → Ca²⁺

What signalling pathway do V1bR (V3) receptors use?

G-protein → PLC → IP₃ → Ca²⁺ _W

Where are V1bR receptors found?

kidney, heart, spleen, anterior pituitary and other parts CNSW

What are the major effects of V1aR receptors?

Increased TPR, factor VIII release, glycogenesis, urea synthesis, male aggressive behaviour

What are the major effects of V1bR (V3) receptors?

ACTH release, aggressive behaviours

Where are V2R receptors located?

kidney, collecting ductsW

What are the major effects of V2R receptors?

water homeostasis, water retention

What signalling pathway do V2R receptors use?

adenylate cyclase → cAMP

What stimulates vasopressin release?

high plasma osmolality

low blood volume/pressure

angiotensin

nicotine

nausea

What inhibits vasopressin release?

low osmolality

high blood volume/pressure

atrial natriuretic peptide

ethanol

How does increased osmolality cause vasopressin release in a cell-autonomous manner?

vasopressin neuron soma shrinks → activates non-selective cation channels = depolarisation → increased firing and VP release

How does decreased osmolality inhibit vasopressin release?

inhibits non-selective cation channels = hyperpolarisation → inhibits AP and reduces VP release

How does vasopressin cause water reabsorption in the kidney?

V2R receptor binding increases cAMP → activates PKA → phosphorylates AQP2 → AQP2 vesicle insertion onto collecting duct membrane → increased water permeability

What channels are inserted into the collecting duct to increase water permeability?

AQP2 vesicles

What are the central effects of vasopressin?

aggression (esp. males)

partner preference and social recognition

learning and memory

What type of receptor is the oxytocin receptor?

G-protein-coupled receptor

Where is the oxytocin receptor expressed?

uterus, mammary glands, testes, kidney, cardiovascular tissue, thymus, CNS

What stimulates oxytocin release?

parturition - signals from uterus, birth canal

lactation - nipple stimulation

genital stimulation

hyperosmolarity(?)

Describe the milk-ejection reflex

baby suckles → stimulates sensory nerve endings in nipple → afferent signalling to brain → activates oxytocinergic hypothalamic neurons → oxytocin release from post. pituitary → myoepithelial muscle contraction → milk ejection

What are the central effects of oxytocin?

female aggression and pair bonding

female reproductive behaviour

What are the effects of oxytocin loss of function?

absent milk-ejection reflex

normal labour

autism - infusion reduced repetitive behaviour

What are oxytocin agonists used for?

induction and enhancement of labour

What are oxytocin antagonists used for?

preventing pre-term labour

prostate hyperplasia

How is diabetes insipidus defined?

>3L dilute urine per 24hrs

What gene mutations are linked to diabetes insipidus?

vasopressin gene

V2 receptor gene

AQP2 gene

What can desmopressin be used to treat?

diabetes insipidus

nocturnal enuresis

von Willebrand’s disease and other haemophilias

What can V2R antagonists treat?

SIADH

congestive heart failure

PCOS

liver cirrhosis

What can V1R antagonists treat?

Raynaud’s

MI

stroke

preterm labour

dysmenorrhoea

glaucoma

(conditions with symptoms from vasoconstriction)