Characterization of peripheral-type benzodiazepine binding sites from rat and pig pancreas.
The binding of [3H]1-(2-chlorophenyl-N-methyl-1-methyl-propyl)-3-isoquinolinecarboxa mide ([3H]PK-11195) and [3H]7-chloro-1,3-dihydro-1-methyl-5-(p-chlorophenyl)-2H-1,4-benzodiaz epin-2 - on ([3H]Ro5-4864) to membrane preparations of pancreas was studied in the rat and pig. [3H]PK-11195 bound with high affinity to rat and pig membrane preparations yielding maximal numbers of binding sites (Bmax) of 2393 +/- 160 and 777 +/- 65 fmol/mg of protein, respectively, and equilibrium dissociation constant (Kd) values of 3.01 +/- 0.25 and 3.9 +/- 0.23 nM, respectively. [3H]Ro5-4864 successfully labelled rat but not pig pancreatic membranes, yielding a Kd value of 6.45 +/- 0.5 nM and a Bmax value of 551 +/- 43 fmol/mg of protein. Displacement studies showed a similar rank order of potency of various unlabelled ligands against both [3H]Ro5-4864 and [3H]PK-11195 binding to rat and pig membrane preparations (PK-11195 > or = Ro5-4864 > diazepam > flunitrazepam >> flumazenil). These results suggest that [3H]PK-11195 binds with high affinity and specificity to rat and pig pancreas and [3H]Ro5-4864 binds with high affinity and specificity to rat but not pig pancreas.
Giusti
L
L
Istituto Policattedra di Discipline Biologiche dell'Università di Pisa, Italy.
Trincavelli
L
L
Martini
C
C
Lucacchini
A
A
D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology*; D001665:Binding Sites; D001667:Binding, Competitive; D002462:Cell Membrane / Q000378:metabolism; D003975:Diazepam / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007546:Isoquinolines / Q000494:pharmacology*; D008297:Male; D010179:Pancreas / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000378:metabolism; D013552:Swine
D001570:Benzodiazepinones; D007546:Isoquinolines; D011963:Receptors, GABA-A; C028513:4'-chlorodiazepam; D003975:Diazepam; C037850:PK 11195