Does Goljan make sense on page 257 of RR path?

[MedStud1984]

So on page 257, goljan says, "aspirin does not inhibit synthesis of PGI2 by endothelial cells."

Later, on that same page, he says "aspirin irreversibly inhibits platelet cyclooxygenase, and prevents the formation of PGH2, the precursor for TXA2."

If aspirin inhibits the COX-1 enzyme, wouldn't PGI2&PGH2 be decreased? Clearly aspirin doesn't inhibit thromboxane synthetase or Prostacyclin Synthase, so what gives? Why one and not the other?

-Medstud1984

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[lipofuscin232]

I think the point to take away from his notes was that aspirin inhibits COX in both platelets and endothelial cells. But since platelets have no nucleus, they can not synthesize any more thromboxane once the enzyme is irreversibly blocked by aspirin, but endothelial cells can still make new prostacyclin...is that what you were asking?

 

[DwyaneWade]

So on page 257, goljan says, "aspirin does not inhibit synthesis of PGI2 by endothelial cells."

Later, on that same page, he says "aspirin irreversibly inhibits platelet cyclooxygenase, and prevents the formation of PGH2, the precursor for TXA2."

If aspirin inhibits the COX-1 enzyme, wouldn't PGI2&PGH2 be decreased? Clearly aspirin doesn't inhibit thromboxane synthetase or Prostacyclin Synthase, so what gives? Why one and not the other?

-Medstud1984

I don't remember exactly why, but in his lecture he says something about how aspirin affects platelets substantially more than the endothelium; hence the greater effect on TXA2 than PGI2

 

[IndyZX]

thats how i learned it during classes... without this concept, it would seem like aspirins effects would mostly cancel out, which isnt what happens.

 

[Lany]

also..

prostacylin's normal fxn is to decrease (inhibit) platelet aggregation through c-amp mech. so and so. whereas thrombaxane's fxn is to increase platelet aggreagation.

so technically aspirin is not the one to inhibit p. aggregation in prostacylin (its jus normal fxn of it). And like AP said, aspirin's effect on the TXA2 is more and in that pathway, TXA2 is directly inhibited thus decrease platelet aggregation.

As for PGI (prostacylin) and PGH ya, both of them should do decrease but its more like.. prostacylin's job of decreasing platelet aggregation gets stopped and even though thats something we dont want, the greater good of inhibiting TXA2 accomplishes our goal. hope that makes sense helps a lil.

 

[medstu2006]

So on page 257, goljan says, "aspirin does not inhibit synthesis of PGI2 by endothelial cells."

Later, on that same page, he says "aspirin irreversibly inhibits platelet cyclooxygenase, and prevents the formation of PGH2, the precursor for TXA2."

If aspirin inhibits the COX-1 enzyme, wouldn't PGI2&PGH2 be decreased? Clearly aspirin doesn't inhibit thromboxane synthetase or Prostacyclin Synthase, so what gives? Why one and not the other?

-Medstud1984

Aspirin irreversibly inhibits COX in both endothelial cells and platelets. However, endothelial cells can synthesize COX and re-gain the synthesis of arachidonic acid by products, while platelets cannot synthesize their own COX.

 

[LUBDUBB]

I don't remember exactly why, but in his lecture he says something about how aspirin affects platelets substantially more than the endothelium; hence the greater effect on TXA2 than PGI2

Ya I 2nd this. I remember that from his lectures too, it affects platlets and not endothelial cells.

 

[Proverbs31]

I think the point to take away from his notes was that aspirin inhibits COX in both platelets and endothelial cells. But since platelets have no nucleus, they can not synthesize any more thromboxane once the enzyme is irreversibly blocked by aspirin, but endothelial cells can still make new prostacyclin...is that what you were asking?

This is correct. (Above) MEDSTUDENT 2006=---sorta has it but it is not considered IRREVERSIBLE inhibition in endothelial cells bc they CAN resynthesize new cyclooxygenase. Its "irreversible" in platelets bc for the remainder of that platelet's life cycle it will not be able to synth cyclooxygenase. More platelets have to be made.

The point as stated above is that - Aspirin inhibits cyclooxygenase. So for the platelets, that strikes them out of the game-they now can no longer make the intermediates leading to the synth of TXA2.

When aspirin is administered it also inhibits the cyclooxygenase in the endothelial cells (they are slightly less sensitive to it--but sensitive nonetheless and their cyclooxygenase becomes inhibited as well. )
Correlation: like Mast cells that secrete preformed Histamine---the endothelial cells will secrete the preformed cyclooxygenase they have and that gets inhibited. Well, now that dose of aspirin is tied up...its taking care of the platelet cyclooxygenase and now the endothelial cells' cyclooxygenase....well Unlike the platelets and similar to the Mast cells the endothelial cells can de-novo synthesize cyclooxygenase (Mast cells denovo synth histamine after the preformed histamine is secreted) ......so they form more and can thus produce the PGI2.

Heres a great Pubmed article on JUST this question. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=371983

Hope that clarifies some things.
🙂