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

Abstract

Prostaglandin D2 (PGD2) and six PGD2 analogues were used to classify responsiveness of several PGD2-sensitive systems. The analogues used were 9 beta-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-15 alpha-hydroxy-delta 5,9,12-prostenoic acid (9-deoxy-delta 9,12-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, 9 beta-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 greater than PGD2 greater than 9 beta-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. 9 beta-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-delta 9,12-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.