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:
- cyclooxyenase inhibitors such as non-steroidal anti-inflammatory drugs (NSAIDs)
- phosholipase A2 inhibitors such as corticosteroids
most PGs are rapidly metabolised by PG 15-OH dehydrogenase (PGDH), mainly in the lungs

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

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⁾
misoprostol
- E1 receptor agonist used to assist in expelling RPOC in miscarriage

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⁾

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

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
- development of abdominal aortic aneurysm (AAA)

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

acts on PG FP receptor
causes uterine contraction and bronchoconstriction
tafluprost
- selective FP receptor agonist used topically to increase uveoscleral outflow in Rx glaucoma

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²⁾