Prostaglandin E1 specific binding in rhesus myometrium

Myometrial low speed supernatant prepared from non-pregnant rhesus uteri was incubated with 3H-Prostaglandin (PG)E1 with or without addition of unlabelled prostaglandins. The uptake of 3H-PGE1 was inhibited in a dose dependent fashion by PGE2greater thanPGE1greater thanPGA1greater thanpgf2alpha=PGA1greater thanPGB1=PGB2greater than or equal toPGD2. PGE1 metabolites inhibited 3H-PGE1 binding in the following order: 13, 14-dihydro-PGE1greater than13,14-dihydro-15-keto-PGE1=15-keto-PGE1. The specific binding of 3H-PGE1 and 3H-PGF2alpha was similarly affected by the temperature and time of incubation. Equilibrium binding constants determined using rhesus uteri obtained during the luteal phase of the menstrual cycle indicate the presence of high affinity PGE1 binding sites with an average (n=3) apparent dissociation constant of 2.2 X 10(-9)M and a lower affinity PGE1 binding site with a Kd approximately equal to 1 X 10(-8)M. No high affinity - low capacity 3H-PGF2alpha sites could be demonstrated. Relative uterine stimulating potencies of some natural prostaglandins and prostaglandin analogs tested after acute intravenous administration in mid-pregnant rhesus monkeys corresponded with the PGE1 binding inhibition of the respective compound. The uterine stimulating potencies of the prostaglandin analogs tested were: (15S)-15-methyl-PGE2=16,16-dimethyl-PGE2greater than17-phenyl-18,19,20-trinor-PGE2greater than16 phenoxy-17,18,19,20-tetranor-PGF2alpha=PGE2=PGE1=(15S)-15-methyl-PGF2alpha greater than PGF2alpha.