Prostaglandins and gene action: possible relevance to the effect of PG system on leukocyte alkaline phosphatase enzyme activity.
Prostaglandin E2, colchicine and imidazole, known to enhance and inhibit thromboxane A2 (TxA2) synthesis respectively and chloroquine, a PGE1 synthesis enhancer and PGE2 antagonist can alter the leukocyte alkaline phosphatase (LAP) enzyme activity. Thromboxane A2 and other related prostaglandins (PGs) are known to bind to DNA and thus possibly regulate DNA action. It is proposed here that prostaglandins are able to modify LAP activity by their action on the DNA and thus the Gene that codes for LAP. This hypothesis envisages that normally there are specific receptors on the genes for PGs. Taking LAP enzyme system as the model, it is proposed that the affinity of TxA1, TxA2, PGE2 and PGE1 to the operator is more than to that of the repressor. But when the levels of TxA2, PGE2 and PGE1 are in excess, all the receptors on the operator are not only completely occupied but they are also able to bind to repressor in sufficient amounts to transiently switch off the LAP synthesis by the structural gene. It is further envisaged that the affinity of the PG receptors on the operator and repressor systems of the operon is greatest for TxA1 and least for PGE2 (TxA1 greater than TxA2 greater than PGE1 greater than PGE2). This hypothesis though simply in its model explains all the variables obtained in our studies on the effect of PGs on the LAP activity. This concept by itself or a suitable modification, may explain the role of PGs in the pathogenesis of cancer. It will be interesting to study, in the light of this hypothesis, the role of the PG system on DNA repair mechanism, m-RNA and t-RNA synthesis and gene action in several systems.
D000469:Alkaline Phosphatase / Q000097:blood / Q000235:genetics*; D000527:Alprostadil; D000818:Animals; D003078:Colchicine / Q000494:pharmacology; D004247:DNA / Q000097:blood; D005796:Genes / Q000187:drug effects; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007962:Leukocytes / Q000187:drug effects / Q000201:enzymology*; D011453:Prostaglandins / Q000494:pharmacology / Q000502:physiology*; D011458:Prostaglandins E / Q000097:blood; D013928:Thromboxane A2 / Q000097:blood
D007093:Imidazoles; D011453:Prostaglandins; D011458:Prostaglandins E; D013928:Thromboxane A2; C029899:imidazole; D004247:DNA; D000469:Alkaline Phosphatase; D000527:Alprostadil; D003078:Colchicine