prostaglandins
Table of Contents
prostaglandins
see also:
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
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
- development of abdominal aortic aneurysm (AAA)
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 06:24 by 127.0.0.1