Peripheral benzodiazepine (BZ) binding sites (PBzS) were characterized on placental expiant membranes. [3H]PK 11195, an isoquinoline carboxamide derivative, which is a ligand specific for PBzS, labeled these sites with an equilibrium dissociation constant of 2.1 nM; the maximal number of binding sites was 396 fmol/mg protein. The effect of various BZ ligands and PK 11195 on the secretion of progesterone (P4) and estradiol-17β (E2) from human term placental explants was studied. Exposure of placental expiants to low doses (10 -8 M) of Ro 5-4864, a BZ ligand which binds with high affinity to PBzS, caused a significant (P < 0.05) increase in the secretion of P4 and E2 into the media (2.4- and 1.4-fold, respectively). On the other hand, high doses (10-5 M) of Ro 5-4864 caused a significant (P < 0.05) decrease in the secretion of P4 and E2 into the media. Also, exposure of expiants to diazepam (10-7 M) and PK 11195 (10-6 M) caused a significant increase in P4 and E2 secretion into the media. In contrast, clonazepam, a BZ ligand specific for the central-type receptors, had no effect on the secretion of either steroid. The combination of diazepam (10-7 M) or Ro 5-4864 (10-8 M) with PK 11195 (10-6 M) did not enhance the stimulatory effects obtained with each agent alone. The effects exerted by Ro 5-4864, PK 11195, and diazepam may be mediated via PBzS.
Bibliographical noteFunding Information:
This work was supported by a grant to E.R.B. from the Lady Davis Foundation and by Grant 87-00234 to M.G. from the U.S.-Israel Binational Science Foundation.
ASJC Scopus subject areas
- Molecular Biology