Different responsiveness of prostaglandin D 2 ‐sensitive systems to prostaglandin D 2 and its analogues

1 Prostaglandin D 2 (PGD 2 ) and six PGD 2 analogues were used to classify responsiveness of several PGD 2 ‐sensitive systems. The analogues used were 9β‐PGD 2 , 5‐(6‐carboxyhexyl)‐1‐(3‐cyclohexyl‐3‐hydroxypropyl)hydantoin (BW245C), 17‐phenyl‐18,19,20‐trinor‐PGD 2 (17‐phenyl‐PGD 2 ), PGD 2 amide, PGD 2 N ‐monomethylamide and 11‐keto‐15α‐hydroxy‐δ 5,9,12 ‐prostenoic acid (9‐deoxy‐δ 9,12 ‐PGD 2 ). The PGD 2 ‐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. 2 PGD 2 , 9β‐PGD 2 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>PGD 2 >9β‐PGD 2 . PGD 2 amide and PGD 2 N ‐monomethylamide were inactive in the former two systems but elicited relaxant activity on the rabbit stomach strip. 17‐Phenyl‐PGD 2 was virtually inactive in the above three systems. 3 PGD 2 and 17‐phenyl‐PGD 2 contracted the guinea‐pig tracheal ring chain and the helical strip of dog cerebral arteries with almost equal potency. 9β‐PGD 2 and BW245C antagonized competitively the contractile action of PGD 2 . PGD 2 amide and PGD 2 N ‐monomethylamide showed weak agonistic actions in the tracheal preparation. 4 9‐Deoxy‐δ 9,12 ‐PGD 2 , showing stronger growth inhibition than PGD 2 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. 5 These results indicate the presence of three groups of PGD 2 ‐sensitive systems that respond differently to PGD 2 and its analogues.