Characterization of [3H]Ro 5-4864 binding sites in rat vas deferens

J Neurochem. 1992 Jan;58(1):39-45. doi: 10.1111/j.1471-4159.1992.tb09274.x.

Abstract

The presence of benzodiazepine binding sites in rat vas deferens was detected using [3H]Ro 5-4864 as a radioligand. The binding of [3H]Ro 5-4864 to the mitochondrial sites is saturable, reversible, and temperature and time dependent. The association rate constant (k1) was 8.7 +/- 0.7 x 10(7) M-1 min-1, and the dissociation rate constant (k-1) was 0.031 +/- 0.003 min-1. The dissociation constant (KD) determined by saturation binding was 5.22 +/- 0.56 nM. The density of binding was 4,926 +/- 565 fmol/mg of protein. The Hill coefficient of binding was 0.99 +/- 0.01, an indication that [3H]Ro 5-4864 binds to a single site. The [3H]Ro 5-4864 binding was inhibited competitively by Ro 5-4864 and 2-hydroxy-5-nitrobenzyl-6-thioguanosine and noncompetitively by PK 11195, nitrendipine, alpha,beta-methylene-ATP, and carboxyatractyloside and was not affected by clonazepam, dicyclohexylcarbodiimide, or protoporphyrin IX. Our data indicate that [3H]Ro 5-4864 binding sites are not identical to those labeled by PK 11195. These binding sites are modulated by the ADP/ATP mitochondrial carrier, and an interaction of dihydropyridines and [3H]Ro 5-4864 binding sites in rat vas deferens is suggested.

MeSH terms

  • Animals
  • Benzodiazepinones / metabolism*
  • Benzodiazepinones / pharmacokinetics
  • Binding Sites / drug effects
  • Binding, Competitive
  • Guanosine / analogs & derivatives
  • Guanosine / metabolism
  • Isoquinolines / pharmacology
  • Male
  • Mitochondria / metabolism
  • Radioligand Assay
  • Rats
  • Rats, Inbred Strains
  • Receptors, GABA-A / metabolism
  • Thionucleosides / metabolism
  • Time Factors
  • Tritium
  • Vas Deferens / metabolism*

Substances

  • Benzodiazepinones
  • Isoquinolines
  • Receptors, GABA-A
  • Thionucleosides
  • Tritium
  • Guanosine
  • 4'-chlorodiazepam
  • 2-hydroxy-5-nitrobenzylthioguanosine
  • PK 11195