2018B15 Describe the physiological role of prostaglandins on smooth muscle throughout the body.

 

List:

·         Intro: prostaglandins

·         Pathway

·         Smooth muscle effects

 

Intro: prostaglandins

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 constriction, GIT smooth muscle dilation

Cellular mechanism

·   Bind to G protein coupled receptors

o Gs : ↑cAMP

o Gi : ↓cAMP

o Gq : ↑IP3/DAG -> ↑Ca2+

 

Pathway:

 

Smooth muscle effects:

Systemic vascular

·   PGI2 vasodilatation (e.g. by vascular endothelium), promotes rapid laminar flow

·   TXA2 vasoconstriction (e.g. ↑release by platelet in tissue injury), assists haemostasis

(low dose aspirin: ↓TXA2 but PGI2 -> ↓risk AMI)

Pulmonary vascular

·   PGD2 -> ↓HPV

·   (Leukotrienes -> ↑HPV)

Renovascular

·   Contributes to hormonal autoregulation of GFR, i.e. renin-angiotensin system

·   ↓NaCl to macula densa -> ↑PGE2, PGI2 release -> ↑renin release

·   (NSAID -> risk of renal impairment, fluid retention)

Airway

·   PGD2, PGF -> bronchoconstriction

·   PGE2 -> bronchodilatation

(corticosteroids -> ↓airway reactivity in asthma)

Uterine

·   PGE2, PGF -> myometrial contraction

·   Important in menstruation, labour

·   Receptors always present cf. oxytocin receptors upregulated at 36/40

(misoprostol and exogenous PGF reduce risk of PPH)

Ureteric

·   PGE2 -> relax

·   PGF -> contract

(NSAID useful in renal colic)

 

 

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