CELL SIGNALING AND

SECOND MESSAGING

General Overview
Communication between cells is essential to
regulate their development, to organize them into
tissues & organs, & to allow normal physiological
processes to take place.
3 main methods:
By the cells secreting chemicals which act at a distance
By forming gap junctions which join the cytoplasm of the
cells
By a cells expression of plasma membrane-bound
molecules, which can affect other cells

Eicosanoid synthesis
Signalling molecules which are continuously
made in the plasma membrane of all
mammaliann tissues
4 major groups:

Prostaglandin
Prostacyclines
Thromboxanes
leukotrienes

Prostaglandins
Important stimulators of myometrium

PGH2 synthase (COX)

COX-1 found in tissues which produce prostaglandins constantly, such
as the stomach mucosa
COX-2 only expressed at sites of inflammation
NSAIDs inhibit COX-1 & or COX-2

 Aspirin
inhibit COX-1 & COX-2
Permanently acetylating the active site of the COX enzyme
At low dose, inhibit platelet tromboxane synthesis with with little effect
upon vascular endothelial prostacyclin synthesis this may be value
in thromboprophylaxis & in the management of pre-eclampsia.
High concentrations of prostanoids have been reported during normal
menstruation & in particular with menorrhagia, dymenorrhea &
endometriosis; all correlate with painful menstruation.
During labour, the fetal membranes are the main source of
prostaglandins
Bacterial product & proinflammatory cytokines can increase expression
of COX-2 & hence prostaglandin synthesis.
Women with intra-amniotic infection have raised pro-inflammatory
cytokines in the amniotic fluid and fetal membranes, although cytokines
are also elevated in spontaneous term labour in the amniotic fluid and
membanes.

Gap junctions
Gap junctions are specialized cell-cell junctions which
form a mirror image of protein units (connexons)
between plasma membranes of cells.
In the myometrium, gap junctions provide lowresistance pathway between the smooth muscles cells,
thereby increasing their electrical coupling to allow
increased coordination of myometrial contractility.
During pregnancy, gap junctions are present at very
low numbers in the mymetrium
Labour is associated with increased numbers and size
of gap junction.

Nitric oxide is an important signalling molecule

NO is produced from L-arginine by the enzyme NO synthase (eNOS,
iNOS, bNOS) in the presence of co-factors & oxygen
Stress/agents NO released from endothelial cells on blood vessels
NO diffuseNO diffuses to the underlying smooth musclereacts
with iron in the active site of the enzyme guanylate cyclase to
produce the intracellular mediator cGMP muscle relaxation.
Continual release of NO from blood vessels main machanisms for
keeping blood pressure
In pregnancy, BP & it is thought that the vasodilatation is partly
mediated by increased NO release
Important in regulating blood flow within the plasenta & eNOS
expressed on the entire syncytiotrophoblast surface to inhibit
aggregation of neutrophils & platelet present in maternal blood in
the intervillous space.

 Inflammation iNOS activate macrophages &

neutrophils NO release from this cells kill invading MO
bNOS from nerve cells
Nitroglycerine is converted to NO relaxes blood vessels in
the heart
GTN breaks down to NO relaxing myometrial smooth
muscle and rippening the cervix prevent pre-term labour