The binding of [3H]-diazepam to guinea-pig ileal longitudinal muscle and the in vitro inhibition of contraction by benzodiazepines.

1--The longitudinal muscle-myenteric plexus strip preparation of the guinea-pig ileum was used to study the binding of [3H]-diazepam and the effect of benzodiazepines on its contraction. 2--Scatchard analysis of binding indicated a single class of binding sites with KD = 43 nM and Bmax = 229 fmol/mg prótein. Binding was of peripheral type based on the much greater binding affinity of Ro5-4864 as compared to clonazepam. Binding of [3H]-diazepam reached equilibrium at 10 min and dissociated rapidly (T1/2 = 1.3 min). The KD 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+, Ca2+, histamine and carbachol. The inhibition of Ca2+-induced contractions was reversed by increasing the concentration of Ca2+ in the medium.