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

· Intro: prostaglandins

· Pathway

· Smooth muscle effects

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 vasoconstriction, PGI₂ vasodilation

· One PG may have different effects on different tissues

o e.g. PGI₂ vasodilation, GIT smooth muscle constriction

Cellular mechanism

· Bind to G protein coupled receptors

o G_s : ↑cAMP

o G_i : ↓cAMP

o G_q : ↑IP₃/DAG -> ↑Ca²⁺

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_2α -> bronchoconstriction · PGE₂ -> bronchodilatation (corticosteroids -> ↓airway reactivity in asthma)
Uterine	· PGE₂, PGF_2α -> myometrial contraction · Important in menstruation, labour · Receptors always present cf. oxytocin receptors upregulated at 36/40 (misoprostol and exogenous PGF_2α reduce risk of PPH)
Ureteric	· PGE₂ -> relax · PGF_2α -> contract (NSAID useful in renal colic)