Where are the v1 (vasopressin 1) and v2 (vasopressin 2) receptors located?

Location of V1 and V2 Vasopressin Receptors

V1a receptors are primarily located on vascular smooth muscle cells and in the myocardium, while V2 receptors are predominantly found in the kidney. 1

V1 Receptor Distribution

V1a Receptors

• Vascular System:

  • Located on vascular smooth muscle cells 1
  • Present in cortical vessels and medullary vessels of the kidney 2
  • Responsible for vasoconstriction effects of vasopressin 1

• Cardiac System:

  • Found in the myocardium 1
  • Contributes to cardiac effects of vasopressin

• Renal System:

  • Partially localized to the glomerulus 2
  • Present in cortical vessels, interstitial cells, and medullary vessels 2
  • Mediates vasoconstriction of medullary vasa recta microvessels 3

V1b Receptors

• Located in the pituitary gland
• Responsible for ACTH release 1

V2 Receptor Distribution

• Renal System:

  • Predominantly found in the kidney 1
  • Specifically localized to collecting ducts and medullary tubules 2
  • Present in principal cells of the collecting duct 4
  • Found in inner medullary collecting duct (IMCD) cells 5
  • Present in some thick ascending limbs 5

• Membrane Distribution:

  • Primarily located on the basolateral membrane of renal tubular cells 5
  • Also found on the luminal membrane of collecting ducts, especially in terminal inner medullary collecting ducts (tIMCD) 5

Functional Significance

V1a Receptor Functions

• Mediates vasoconstriction, particularly in vascular smooth muscle 1
• Reduces blood flow to inner medulla of the kidney 3
• This reduction in medullary blood flow is necessary to optimize urine osmolality during water restriction 3

V2 Receptor Functions

• Mediates anti-diuretic effects of vasopressin 1
• Responsible for three main effects on principal cells of the collecting duct 4:
  1. Increases water permeability along the entire collecting duct (via AQP2 water channels)
  2. Increases urea permeability in the terminal inner medullary collecting duct (via UT-A1)
  3. Stimulates sodium reabsorption, mainly in the cortical and outer medullary collecting duct (via ENaC)

Clinical Relevance

• V2 receptor antagonists like tolvaptan are used for treating hyponatremia associated with heart failure, cirrhosis, and SIADH 6
• V1a receptor activation in vascular smooth muscle induces vasoconstriction that is catecholamine-independent, which explains why vasopressin complements norepinephrine in septic shock 1
• Highly selective V1a agonists may have better effects in septic shock than vasopressin due to their narrow focus on the V1a receptor 1

Interaction Between V1a and V2 Receptors

• Vasopressin-induced vasoconstriction via V1a receptors is normally modulated by vasopressin-stimulated release of nitric oxide (NO) through V2 receptor stimulation 3
• This interaction helps provide a constancy of blood flow to the renal medulla and buffers against the hypertensive actions of vasopressin 3
• Luminal V2 receptors in terminal inner medullary collecting ducts can inhibit the effects of basolateral V2 receptor activation, acting as a negative feedback system 5

Understanding the distribution and function of these receptors is crucial for comprehending the physiological effects of vasopressin and for developing targeted therapies for conditions like hyponatremia, heart failure, and septic shock.