Abstract:
:Peripheral benzodiazepine (BZ) binding sites (PBzS) were characterized on placental explant 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-17 beta (E2) from human term placental explants was studied. Exposure of placental explants to low doses (10(-8) M) of Ro 5-4864, a BZ ligand which binds with high affinity to PBzS, caused a significant (P less than 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 less than 0.05) decrease in the secretion of P4 and E2 into the media. Also, exposure of explants 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.
journal_name
Mol Cell Endocrinoljournal_title
Molecular and cellular endocrinologyauthors
Barnea ER,Fares F,Gavish Mdoi
10.1016/0303-7207(89)90141-xsubject
Has Abstractpub_date
1989-07-01 00:00:00pages
155-9issue
2eissn
0303-7207issn
1872-8057journal_volume
64pub_type
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