Peripheral benzodiazepine binding sites in Nb 2 node lymphoma cells: effects on prolactin-stimulated proliferation and ornithine decarboxylase activity.
[3H]Ro 5-4864 binds to Nb 2 node lymphoma cells in a specific saturable and reversible fashion. Scatchard analysis of specific binding data reveals a single, homogeneous class of whole cell binding sites with a Kd of 3.94 +/- 0.22 nM and a Bmax value of 155 +/- 11 fmol (Ro 5-4864 bound)/2 x 10(6) cells. Ro 5-4864, a reported peripheral benzodiazepine receptor agonist both inhibits (10(-6) M) and potentiates (10(-9) M) the mitogenic action of prolactin on the Nb 2 node lymphoma cells. Interestingly, PK 11195, an antagonist, potentiates (10(-9) M) the mitogenic activity of prolactin in these cells. The actions of both Ro 5-4864 and PK 11195 seem to be mediated through a common receptor type since a 10(-6) M concentration of either agent will block the others potentiating action. Furthermore, the simultaneous addition of a 10(-9) M concentration of Ro 5-4864 and PK 11195 does not further increase the effect on prolactin stimulated mitogenesis. Clonazepam, a central benzodiazepine receptor agonist has no effect on prolactin-stimulated mitogenesis in this system. These data suggest that the Nb 2 node lymphoma cells possess a peripheral-type benzodiazepine receptor. In these cells, this receptor seems to serve the function of modulating the ability of the growth factor, prolactin to initiate the mitogenic process. These studies also suggest that Ro 5-4864 is functioning as a partial agonist rather than a 'pure' agonist for the peripheral benzodiazepine receptor in this system.
Laird
H E
HE
Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona, Tucson, 85721.
Gerrish
K E
KE
Duerson
K C
KC
Putnam
C W
CW
Russell
D H
DH
D001570:Benzodiazepinones / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002998:Clonazepam / Q000494:pharmacology; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology; D007700:Kinetics; D008198:Lymph Nodes / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D008223:Lymphoma / Q000201:enzymology / Q000378:metabolism*; D009955:Ornithine Decarboxylase / Q000378:metabolism*; D011388:Prolactin / Q000494:pharmacology*; D011963:Receptors, GABA-A / Q000378:metabolism*; D013936:Thymidine / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D001570:Benzodiazepinones; D007546:Isoquinolines; D011963:Receptors, GABA-A; C028513:4'-chlorodiazepam; D002998:Clonazepam; D011388:Prolactin; D009955:Ornithine Decarboxylase; D013936:Thymidine; C037850:PK 11195