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

• Published in: British journal of pharmacology 1983-02, Vol.78 (2), p.321-327
• Main Authors: Hullihan, John P., Spector, Sydney, Taniguchi, Takashi, Wang, James K. T.
• Format: Article
• Language: English
• Subjects: Animals; Anti-Anxiety Agents - pharmacology; Binding, Competitive; Carbachol - pharmacology; Diazepam - metabolism; Electric Stimulation; Guinea Pigs; Histamine - pharmacology; Ileum - metabolism; In Vitro Techniques; Kinetics; Muscle Contraction - drug effects; Muscle, Smooth - drug effects; Muscle, Smooth - metabolism; Potassium Chloride - pharmacology
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1111/j.1476-5381.1983.tb09397.x

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 protein. 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.