CELL SIGNALING AND

SECOND MESSAGING

& to allow normal physiological processes to take place. which can affect other cells . to organize them into tissues & organs.General Overview • Communication between cells is essential to regulate their development. • 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 cell’s expression of plasma membrane-bound molecules.

Eicosanoid synthesis • Signalling molecules which are continuously made in the plasma membrane of all mammaliann tissues • 4 major groups: • • • • Prostaglandin Prostacyclines Thromboxanes leukotrienes .

such as the stomach mucosa • COX-2  only expressed at sites of inflammation • NSAIDs inhibit COX-1 & or COX-2 .Prostaglandins • Important stimulators of myometrium • PGH2 synthase (COX) • COX-1  found in tissues which produce prostaglandins constantly.

although cytokines are also elevated in spontaneous term labour in the amniotic fluid and membanes. dymenorrhea & endometriosis. • Women with intra-amniotic infection have raised pro-inflammatory cytokines in the amniotic fluid and fetal membranes. • During labour. the fetal membranes are the main source of prostaglandins • Bacterial product & proinflammatory cytokines can increase expression of COX-2 & hence prostaglandin synthesis. all correlate with painful menstruation. . • High concentrations of prostanoids have been reported during normal menstruation & in particular with menorrhagia.• 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.

. • In the myometrium. 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. gap junctions provide lowresistance pathway between the smooth muscles cells.Gap junctions • Gap junctions are specialized cell-cell junctions which form a mirror image of protein units (connexons) between plasma membranes of cells.

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 musclereacts 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.Nitric oxide is an important signalling molecule • NO is produced from L-arginine by the enzyme NO synthase (eNOS. iNOS. .

• 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 .