Pharmacology of the uterus Flashcards
what are the 3 layers of the uterus?
1)endometrium
2)myometrium
3)perimetrium
what muscle is the myometrium made of?
smooth muscle
what are the 3 fibres that make up the myometrium?
1)Outer=longitudinal
2)Middle= Figure-eight fibres
3)Inner= Circular fibres
what occurs at all 3 layers of the fibres of the myometrium and what does this cause during labor?
They contract, causing an increase in the uterus pressure, increasing the pressure that’s put on the uterus, therefore pushing the baby out.
what is the mechanical property of the myometrium? and what does this mean?
Myogenic contractility- it can contract spontaneously without any external stimuli, contracting without any neuronal or hormonal input.
what his the role of Interstitial cells of Cajal (ICC’s)?
Act as pace maker cells in the myometrium
what do ICC’s look like?
brown line between smooth muscle cells.
what are connexin proteins?
Gap junction proteins. They are a family of trans-membrane proteins that allow intracellular communication and the transfer of ions and small signalling molecules between cells.
Briefly describe what happens during sympathetic release of noradrenaline.
Sympathetic release of noradrenaline causes a contractile slow wave of electrical activity coming from the ICC to increase contractility. Gap junctions (ion channels) and connexion proteins expressed in adjacent cells form a gap junction for electrical coupling which you get after the ICC forms the electrical signal, coupled to gap junctions. Smooth muscle cells contract together
where do gap junctions occur? (4)
1)Between ICCs
2)Between ICCs and smooth muscle cells
3)Between smooth muscle cells
4)Function as a synctium
what do ICCs and smooth muscle cells work together as?
A synctium
what modulates the slow wave of ICC and smooth muscle responses?
Neurotransmitters and hormones
What are ICC and smooth muscle responses sensitive to?
Sex hormones e.g Oestrogen and Progesterone.
Describe in detail the cellular mechanism of smooth muscle contraction.
1) You have G protein coupled receptors, which is coupled to phospholipase c enzyme
2)On binding of an agonist/ ligand, you have the PLC enzyme cleaving PIP into IP3 and DAG.
3)IP3 binds to its receptors on the sarcoplasmic reticulum, which causes calcium to be released from the sarcoplasmic reticulum
4)DAG binds to membrane receptors, which causes a a calcium influx into the cell
5)This causes depolarisation of the cell and causes activation of the voltage gated calcium channels, causing an influx of Ca2+
6)Ca2+ binds to calmodulin, which causes activation of the Myosin light chain kinase to phosphorylated light chain. This causes myosin to straighten and interact with actin
7)We get contraction
Does the increase in Ca2+ have a linear relationship with the force of contraction?
No
what causes the contraction of smooth muscle?
Calcium
what are the 3 mechanisms of lowering the calcium lvls in extrusion?
1)Calcium pump to mitochondria
2) Calcium ATPase pump
3)Sodium Calcium exchanger
what does low concentrations of stimulants on ICCs cause?
An increased slow wave frequency producing an increased frequency of contraction
what does higher concentrations of stimulants on ICCs cause?
Increased frequency of action potentials on top of slow waves (increased calcium conc peak), producing both an increased frequency and force of contraction.
what does a continued higher concentration of stimulants on ICCs cause?
An increased plateau of slow wave producing prolonged sustained contractions
What does a large concentration of stimulants on ICC cause?
1)Hypertonus (contraction occurs for a longer duration so relaxation period is shorter)
2)This occurs as a result of calcium extrusion processes not being effective
what is the effect of large concentrations of stimulants on ICC in the myometrium to the infant?
This means that the duration of contrition is longer, which interferes with the blood flow, minimising blood loss resulting in foetal distress as the baby isn’t receiving enough O2 through the placenta.
Is there sympathetic or parasympathetic innervation in the myometrium?
Sympathetic
what causes the sympathetic innervation at the myometrium?
Neurotransmitters
expression of what adrenoreceptors are located at the myometrium? and what occurs here?
1)Alpha-1 adrenoreceptors= adrenaline/noradrenaline binds here to cause=Contraction
2)Beta-2 adrenoreceptors= Adrenaline/noradrenaline binds here to cause relaxation
What type of protein are alpha adrenoreceptos? and what occurs here that leads to contraction? (simple)
G protein coupled receptors-It is a Gq type
At the Gq type protein once agonist binds to the alpha adrenoreceptor= activation of Phospholipase C, increasing IP3 and DAG, ultimately increasing intracellular ca2+ conc, leading to smooth muscle contraction and glycogenolysis.