User Tools

Site Tools


prostaglandins

prostaglandins

introduction

  • prostaglandins are substances derived from membrane phospholipids via the actions of the enzymes phosholipase A2, phospholipase C and then cyclooxygenase
  • these metabolic products of phospholipids and arachidonic acid are autacoids forming the prostanoid class of fatty acid derivatives (and these also include thromboxane and the leukotrienes) which are a subclass of eicosanoids including prostaglandins
  • every prostaglandin contains 20 carbon atoms, including a 5-carbon ring.
  • they have a variety of critically important roles in physiology
  • they have key roles in the physiology of inflammation
  • it is thought that COX-1 synthesises baseline levels of PG's while COX-2 activity is increased during inflammation
  • PG production is inhibited by:
  • most PGs are rapidly metabolised by PG 15-OH dehydrogenase (PGDH), mainly in the lungs

prostaglandin PG E2

  • produced from PG H2 via PGE synthase
  • acts on a variety of PG E receptors as below plus
    • causes hyperalgesia and fevers
    • appears to help maintain urine output when renal blood flow is decreased

PG E1 receptor

  • bronchoconstriction
  • contraction of pulmonary venous smooth muscle
  • GIT smooth muscle contraction
  • induces contractions of the smooth muscle fibers in the myometrium and relaxation of the uterine cervix
  • may play roles in:
    • inhibition of sleep
    • regulation of peripheral circadian clock
    • renal vasoconstriction 1)
    • E1 receptor agonist used to assist in expelling RPOC in miscarriage

PG E2 receptor

  • bronchodilation
  • GIT smooth muscle relaxation
  • vasodilatation
  • increased renin secretion via direct effect on JG cells
  • decreased ADH mediated reabsorption of water
  • downregulation of protease-activated receptors (PARs)
  • promotion of cell growth such as chondrocytes
  • inhibition of TNFα release from alveolar macrophages
  • reduction of intraocular pressure
  • augmentation of G-CSF secretion and suppression of GM-CSF release from airway smooth muscle cells
  • ?role in carcinogenesis in prostate cancer2)

PG E3 receptor

  • decreases gastric acid secretion
  • increases gastric mucus secretion
  • GIT smooth muscle contraction
  • uterine contraction in pregnancy
  • inhibits lipolysis
  • increases autonomic neurotransmitters
  • increases platelet response
  • increases atherothrombosis
  • may be involved in:
    • mediation of adrenocorticotropic hormone response
    • fever generation

PG E4 receptor

  • activates T-cell factor signaling
  • suppresses the release of cytokines and chemokines from macrophages and T-cells
  • induces expression of early growth response 1 (EGR1),
  • regulates the level and stability of cyclooxygenase-2 mRNA
  • phosphorylation of glycogen synthase kinase-3
  • vasodilation
  • bronchodilation
  • inhibition of platelet aggregation
  • negatively regulates aberrant synovial overgrowth and the development of osteoclast activity in rheumatoid arthritis
  • inhibition of LPS-induced mucus secretion from airway epithelial cells
  • may be involved in:
    • neonatal adaptation of circulatory system incl. closure of ductus arteriosus
    • osteoporosis
    • initiation of skin immune responses
    • promotion of sleep

prostacyclin (PG I2)

  • acts on the PG IP receptor
  • vasodilation
  • inhibits platelet aggregation
    • PG I2 released from endothelium presumably is the physiologic antagonist of thromboxane A2 for platelet aggregation
  • bronchodilation
  • augmentation of glucocorticoid-induced gene expression
  • inhibition of chemokine release

prostaglandin PGF2alpha

  • acts on PG FP receptor
  • causes uterine contraction and bronchoconstriction
  • tafluprost
    • selective FP receptor agonist used topically to increase uveoscleral outflow in Rx glaucoma
prostaglandins.txt · Last modified: 2013/10/10 17:24 (external edit)