Different responsiveness of prostaglandin D2‐sensitive systems to prostaglandin D2 and its analogues

Publisher Website
Google Scholar
Abstract
Prostaglandin D2 (PGD2) and six PGD2 analogues were used to classify responsiveness of several PGD2‐sensitive systems. The analogues used were 9β‐PGD2, 5‐(6‐carboxyhexyl)‐1‐(3‐cyclohexyl‐3‐hydroxypropyl)hydantoin (BW245C), 17‐phenyl‐18,19,20‐trinor‐PGD2 (17‐phenyl‐PGD2), PGD2 amide, PGD2 N‐monomethylamide and 11‐keto‐15α‐hydroxy‐δ5,9,12‐prostenoic acid (9‐deoxy‐δ9,12‐PGD2). The PGD2‐sensitive systems examined were human platelets, rat peritoneal mast cells, rabbit transverse stomach strip, guinea‐pig tracheal ring chain and helical strip of the dog cerebral artery. PGD2, 9β‐PGD2 and BW245C inhibited the aggregation of human platelets, increased adenosine 3′:5′‐cyclic monophosphate (cyclic AMP) in rat mast cells and relaxed the rabbit stomach strip. The rank order of potency was BW245C>PGD2>9β‐PGD2. PGD2 amide and PGD2 N‐monomethylamide were inactive in the former two systems but elicited relaxant activity on the rabbit stomach strip. 17‐Phenyl‐PGD2 was virtually inactive in the above three systems. PGD2 and 17‐phenyl‐PGD2 contracted the guinea‐pig tracheal ring chain and the helical strip of dog cerebral arteries with almost equal potency. 9β‐PGD2 and BW245C antagonized competitively the contractile action of PGD2. PGD2 amide and PGD2 N‐monomethylamide showed weak agonistic actions in the tracheal preparation. 9‐Deoxy‐δ9,12‐PGD2, showing stronger growth inhibition than PGD2 on cultured tumour cells, was inactive in human platelets, rat mast cells and guinea‐pig trachea, and elicited contractile response in the rabbit stomach strip. These results indicate the presence of three groups of PGD2‐sensitive systems that respond differently to PGD2 and its analogues.

This publication has 31 references indexed in Scilit: