2011B09 Outline the physiological roles of prostaglandins in the body.

 

List:

        Intro

        Pathway

        The big 3

        Body systems

 

Intro:

Definition

   Lipid mediators derived from arachidonic acid

   Production induced by cyclo-oxygenase

o COX-1: constitutive, for homeostasis

o COX-2: inducible, for inflammation etc

Actions

   Autocrine and/or paracrine

   Inhibitory or excitatory

   Two PGs may have opposing effects at the same tissue

o e.g. TXA2 vasoconstrict, PGI2 vasodilate

   One PG may have different effects on different tissues

o e.g. PGI2 vascular smooth muscle dilation, GIT smooth muscle constriction

Cellular mechanism

   Bind to G protein coupled receptors

o Gs : ↑cAMP

o Gi : ↓cAMP

o Gq : ↑IP3/DAG -> ↑Ca2+

 

Pathway:

 

The big 3:

Inflammation

   WBC -> cytokines (TNFα, IL1, IFN) -> ↑activity iNOs -> ↑NO -> ↑activity of COX-2

   ↑production of PGD2, PGE2

   Vasodilation, cap leak, chemotaxis, mast cell degranulation, promotion of T cell differentiation

Pain

   Causes nociception, hyperalgaesia, allodynia

   Inflamed tissue, WBC -> prostaglandin -> nociceptor activation and sensitization

   Sensitised nociceptor -> substance P, NKA -> inflammation

   Note vicious cycle

Pyrexia

   PGE2 in hypothalamus -> ↑temp set point ->fever

   Production induced by cytokines (TNFα, IL-1), other

 

Body systems:

Cardiovascular

   PGI2: local vasodilatation

   TXA2: local vasoconstriction

   Role in HPV unclear

Respiratory

   Bronchial smooth muscle: PGD2 and PGF constriction, PGE2 dilation

   Pulmonary vasculature: role in HPV unclear

Renal

   Renin-angiotensin: ↓NaCl load to DT -> ↑PGE2, PGI2 release -> ↑renin release

   i.e. hormonal autoregulation of GFR

Gastrointestinal

   Activity of mucus neck cells: mucus, HCO3- (note COX-1 only)

Haematological

   PGI2: ↓platelet aggregation

   TXA2: ↑platelet aggregation

Genitourinary

   PGE2, PGF: myometrial contraction

   Important in menstruation and in labour

   Receptors always present cf. oxytocin