Premium
The binding of [ 3 H]‐diazepam to guinea‐pig ileal longitudinal muscle and the in vitro inhibition of contraction by benzodiazepines
Author(s) -
Hullihan John P.,
Spector Sydney,
Taniguchi Takashi,
Wang James K. T.
Publication year - 1983
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1983.tb09397.x
Subject(s) - diazepam , guinea pig , contraction (grammar) , in vitro , muscle contraction , pharmacology , chemistry , chlordiazepoxide , endocrinology , medicine , biochemistry
1 The longitudinal muscle‐myenteric plexus strip preparation of the guinea‐pig ileum was used to study the binding of [ 3 H]‐diazepam and the effect of benzodiazepines on its contraction. 2 Scatchard analysis of binding indicated a single class of binding sites with K D = 43 n m and B max = 229 fmol/mg protein. Binding was of peripheral type based on the much greater binding affinity of Ro5–4864 as compared to clonazepam. Binding of [ 3 H]‐diazepam reached equilibrium at 10 min and dissociated rapidly ( T 1/2 = 1.3 min). The K D derived from the rate constants agreed with that from the Scatchard analysis. 3 Benzodiazepines produced a dose‐dependent decrease in the electrically induced contractions of the longitudinal muscle strip, but their potencies in this effect did not correlate with their binding affinities. 4 Diazepam antagonized the contractions of the longitudinal muscle strip induced by K + , Ca 2+ , histamine and carbachol. The inhibition of Ca 2+ ‐induced contractions was reversed by increasing the concentration of Ca 2+ in the medium.