Pharmacology of the Uterus Flashcards
Describe the structure of the myometrium
- Outer longitudinal fibres
- Middle figure-eight fibres
- Inner circular fibres
What does contraction of the myometrium do?
Increase in uterine pressure, forcing content towards the cervix and acts as a natural ligature to prevent blood lost.
What type of muscle is the myometrium?
Spontaneously active - myogenic
Produces regular contractions without neuronal or hormonal input
What is the myometrium sensitive to?
It is highly sensitive to neurotransmitters and hormones
Why does the myometrium contract rhythmically?
It contractions rhythmically for parturition
How is synchronous contraction achieved?
By pacemaker cells in the myomterium - the interstitial cells of cajal (ICCs) that initiate and coordinate contractions
- Electrical communication via gap junctions made of connexion proteins
Where are the gap junctions located and what do they do?
- Between ICCs
- Between ICCs and smooth muscle cells
- Between smooth muscle cells
- Function as a syncytium
Describe the electrical activity of the myometrium
ICC periodic activation of inward currents which causes depolarisation. Calcium enters via VGCCs and increases intracellular calcium levels and causes contraction.
What modulates the slow waves of ICCs and smooth muscle responses?
Neurotransmitters and hormones
Briefly describe the mechanism of smooth muscle contractions
- Oxytocin or another substance binds to a GCPR q/11.
- IP3 binds to SR and causes release of Calcium and increases intracellular calcium
- DAG activates ion channels.
- Action of ion channels increases membrane excitability
- Causes depolarisation
- Activates VGCCs which induces Ca2+ influx
- Increase of intracellular calcium
- Activates calmodulin, activates myosin light chain kinase that cause the reaction between the myosin head and the actin.
- This causes contraction
What is the graded response of calcium?
Incremental increases in calcium -> incremental increases in force of contraction
What is excitation - contraction coupling?
- Increase in slow wave frequency producing high frequency of contractions
- Increase in frequency of action potentials on top of slow waves producing both high frequency and force of contractions
- Increase plateau of slow wave producing prolonged sustained contractions
- Hypertonus
- Ca2+ extrusion processes not effective
What is hypertonus?
It is incomplete relaxation
What type of innervation does the myometrium receive?
Sympathetic innervation
What receptors does the myometrium express?
Express:
- Alpha-adrenoreceptors
- Beta adrenoreceptors
What do alpha adrenoreceptor agonists cause?
Contraction
What does beta adrenoreceptors cause?
Relaxation
What does progesterone do on the myometrium?
It inhibits contraction
What does oestrogen do on the myometrium?
It increases contraction
Describe the regulation of the myometrium via sex hormones during non-pregnancy
Weak contractions early in the cycle
Strong contractions during menstruation (low progesterone, high prostaglandins)
Describe the regulation of the myometrium via sex hormones during pregnancy
Weak and uncoordinated in early pregnancy (high progesterone)
Strong and co-ordinated at parturition (high oestrogen)
What increases during parturition?
Oestrogen/Progesterone ratio increases
Oestrogen increases while progesterone decreases gap junction expression in myometrium
Oestrogen/Progesterone receptors are also found on ICCs
What does the myometrium and endometrium synthesise?
They synthesise prostaglandins: PGE2 and PGF2a - promoted by oestrogens.