Prostacycline PGI

Eicosanoids These compounds, derived from eicosa- (20-carbon) polyenoic fatty acids, comprise the prostanoids, leukotrienes (LTs), and lipoxins (LXs). Prostanoids include prostaglandins (PGs), prostacyclins (PGIs), and thromboxanes (TXs). 

Prostacyclin (PGI) activates adenyl cyclase. Increase in cAMP lowers calcium levels and... 

Peripheral vascular diseases Infusion or intraarterial injection of prostacyclin (PGI ) improves potency of blood vessels in certain peripheral vascular diseases. Infusion of PGI can also reduce the infarct size in immediate postmyocardial infarction period. 

TXA ) from platelets promote and prostacyclin (PGI ) from vessel wall inhibit platelet aggregation. 

Cox-1 is constitutively expressed and responsible for most of the housekeeping functions of eicosanoids, including processes such as calcium metabolism in the bone, and stomach mucous membrane maintenance. It is also responsible for synthesis of thromboxanes in thrombocytes and of prostacyclin (PGI) in endothelial cells, which have antagonistic function in thrombocyte aggregation and activation (see later). 

PG synthesis involves four steps (Figme 2). The first two steps are common to all cells involved in prostaglandin synthesis while the final two steps are cell-specific (14-16). Release of the substrate, arachidonic acid, from membrane phospholipid stores by phospholipase is the initial event in prostaglandin synthesis, and this is followed by formation of the common PG intermediate, PGHj catalyzed by PGH synthase. At this point, rearrangement of PGH to form either stabk (PGD / Ej/ F, ) or unstable (platelet thromboxane - TxA, endothelial prostacyclin - PGy products takes place. The final step, also cell-specific, involves breakdown of the active compounds to irractive metabolites. 

The eicosanoids—prostaglandins (PGs), thromboxanes (TXs), prostacyclins (PGIs), and leukotrienes (LTs)—are derived from essential fatty acids and act similarly to hormones (Chapter 30). However, they are synthesized in almost all tissues (unlike hormones, which are synthesized in selected tissues) and are not stored to any significant extent their physiological effects on tissues occur near sites of synthesis rather than at a distance. They function as paracrine messengers and are sometimes referred to as autacoids. 

Ring structures of prostaglandins (PG), prostacyclin (PGI), and thromboxane (TXs). Groups that lie behind the plane of the ring are shown by 111 and those that lie above the plane by <. 

Fig. 35.5. Ring substituents of the prostaglandins (PG). The letter after PG denotes the configuration of the ring and its substituents. R4, R7, and Rg represent the non-ring portions of the molecule. R4 contains four carbons (including the carboxyl group). Ry and Rg contain seven and eight carbons, respectively, and correspond to the 1-, 2-, or 3-series shown in Figure 35.6. Note that the prostacyclins (PGI) contain two rings.

Dialysis Prostacyclin (PGy is approved for use (as epoprostenol) in severe pulmonary hypertension. It has occasionally been used to prevent platelet aggregation in dialysis machines. 

Hedqvist, P. (1979). Actions of prostacyclin (PGI ) on adrenergic neuroeffector transmission in the rabbit kidney. Prostaglandins, 17, 249-258... 

Prostaglandins (PG) produced by the uterus have several roles in reproduction, for example, luteolysis, menstruation, implantation and parturition. Up to 1976, all the experimental evidence indicated that the major prostaglandin produced by the uterus was PGFgQ (1). However, studies on the pseudopregnant rat uterus around that time revealed that 6-oxo-PGF 0, now known to be the more stable metabolite of prostacyclin (PGI c ),was the major prostaglandin synthesised by the broken cell preparation (2). For our studies on the uterus, therefore, it became essential to develop an assay for measuring 6-oxo-PGF accurately and precisely. This paper described the development of a radioimmunoassay (RIA) for measuring 6-oxo-PGF Parts of this work have been reported previously (3,4). 

The anti-aggregatory response was prevented by addition of an antibody directed against 5,6-dihydro-prostacyclin (PGI ) which also effectively binds prostacyclin (9) (Fig. ID). 

Fig. 13.3 Arachidonic acid (AA) is metabolized by cy- (TXA ), PGEj, and prostacyclin (PGI ) by thromboxane clooxygenase (COX) to prostaglandin (PG) Gj that rear- synthase (TXAS), PGEj synthase (PGES), and prostacy-ranges to PGHj. PGHj is metabolized to thromboxane Aj clin synthase (PTGIS), respeetively...

CHEMICAL SYNTHESIS Prostaglandins E and F Prostaglandins A, C and D Prostacyclins (PGI) and thromboxanes Prostaglandin analogues... 

The literature on the synthesis of prostaglandins is now very substantial, the number of published papers having increased some eight-fold since the last review [ 1 ]. Major advances have included new and improved syntheses of the primary (E and F) prostaglandins, syntheses of PGs A, C and D, thromboxane Bi and prostacyclin (PGI), and the preparation of numerous prostaglandin analogues. Selected references are included here with the object of illustrating the main trends in this work. 

The spreading applications of prostanoids-especi-ally that of the prostacyclin, the effective antiplatelet and cytoprotective agent - is limited by their instability To overcome this problem either ne tf, more stable aiialogues are synthetized, or the endogeneous substance is stabilized by cyclodextrin complexation / /. The rates of hydroly-sis of prostacyclin /PGI / and its methyl-ester /PGI Me/ in aqueous solution are significantly retarded by c(-, p-and jj -cyclodextrin /8/ The highest stability constant could be rendered to PGI Me-(S-CD complex ... 

The involvement of prostanoids in the vascular system spans from their involvement in platelet aggregation, hemostasis and thrombosis, to the regulation of the vascular tone and mediation of many vascular pathologies. One pair of prostanoids, TXA, and prostacyclin (PGI ), play an essential role in... 

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