On the molecular structure of some prostaglandin receptors.

Abstract

Hypotheses are presented of the detailed molecular structure of two prostaglandin receptors both concerned in tumor-promotion processes. These structures have been derived by the comparison of the molecular structure of agents active at the site with (i) a simple theoretical protein structure and (ii) the known x-ray structure of phospholipase A2. The first model receptor is stimulatory to the tumor-promotion process and may be located on the control system for ornithine decarboxylase. The binding of PG here is cooperative with the binding of Ca++. Naturally-occurring agonists at this receptor may include members of the cathartic class of drugs such as colocynth, chrysarobin, etc. Naturally-occurring antagonists at this site may include a number of anti-tumor compounds such as datiscoside. The second model receptor (PGE1) is inhibitory to the tumor-promotion process and is located at a specific allosteric site on the x-ray-determined structure of phospholipase A2. This site overlaps for one for lysolecithin (excitatory), for which tumor-promoting phorbol esters such as TPA are agonists and some anti-tumor drugs such as maytansine may be antagonists.

• Authors: J R Smythies
• Journal: Prostaglandins and medicine (Prostaglandins Med) Vol. 2 Issue 5 Pg. 393-400 (May 1979) ISSN: 0161-4630 [Print] United States
• PMID: 233033 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Carcinogens
• Prostaglandin Antagonists
• Prostaglandins E
• Receptors, Cell Surface
• Receptors, Prostaglandin
• Phospholipases A
• Phospholipases A2
• Calcium

Topics

• Antineoplastic Agents (pharmacology)
• Binding Sites
• Calcium (metabolism)
• Carcinogens (pharmacology)
• Chemical Phenomena
• Chemistry
• Models, Biological
• Phospholipases A
• Phospholipases A2
• Prostaglandin Antagonists
• Prostaglandins E
• Receptors, Cell Surface
• Receptors, Prostaglandin