Interactions between prostaglandin analogues and a receptor in bovine Corpora lutea. Correlation of dissociation constants with luteolytic potencies in hamsters.
The dissociation constants for the interactions between some prostaglandin analogues and a prostaglandin F2 receptor in bovine corpora lutea were determined. These values were compared to the antifertility potencies of these compounds in hamsters and the rates of metabolism by 15-hydro-syprostaglandin dehydrogenase. The most active analogues with regard to both affinity for the receptor and luteolytic potency were 17-phenyl-18, 19, 20-trinorprostaglandin F2alpha and 15-methylprostaglandin F2alpha. The alkyl side chain of prostaglandins could be modified considerably without altering the affinity for the receptor. In this way metabolism by 15-hydroxyprostaglandin dehydrogenase could be blocked. Some of these compounds -ad greatly increased luteolytic effects. Substitution of a phenyl group for the 3 terminal carbon units of the alkyl side chain of prostaglandins increased both the affinity for the receptor and the luteolytic activity in vivo. 7-oxa-13-prostynoic acid, an antagonist of the luteolytic effect of prostaglandin F2alpha in vivo was a weak competitive inhibitor of the interation between prostaglandin F2alpha and the receptor.
D000818:Animals; D001665:Binding Sites; D001681:Biological Assay; D002417:Cattle; D003338:Corpus Luteum / Q000378:metabolism*; D006224:Cricetinae; D005260:Female; D005298:Fertility / Q000187:drug effects; D007700:Kinetics; D011453:Prostaglandins / Q000378:metabolism* / Q000494:pharmacology; D011458:Prostaglandins E / Q000378:metabolism; D011459:Prostaglandins E, Synthetic; D011460:Prostaglandins F / Q000378:metabolism; D011461:Prostaglandins F, Synthetic; D011485:Protein Binding; D011955:Receptors, Drug; D013329:Structure-Activity Relationship
D011453:Prostaglandins; D011458:Prostaglandins E; D011459:Prostaglandins E, Synthetic; D011460:Prostaglandins F; D011461:Prostaglandins F, Synthetic; D011955:Receptors, Drug