Effects of benzodiazepines on responses of guinea-pig ileum and gall-bladder and rat pancreatic acini to cholecystokinin.

Bradwejn and De Montigny have recently shown that benzodiazepines selectively inhibit excitation of hippocampal neurones by cholecystokinin (CCK). We show here that lorazepam and chlordiazepoxide selectively inhibit the nerve-mediated response of ileal longitudinal muscle to CCK, but have no effect on the direct stimulation of gall-bladder muscle or pancreatic acini by this peptide. Lorazepam (1 and 10 microM) and chlordiazepoxide (0.1 and 1 microM) inhibited responses of guinea-pig ileum, but not gall-bladder to CCK. Responses of both tissues to acetylcholine (ACh) were unaffected and lorazepam (10 microM) did not inhibit ileal responses to neurotensin, 5-hydroxytryptamine and substance P which act entirely or in part by stimulating myenteric nerves. Chlordiazepoxide (1 and 10 microM) did not inhibit CCK-stimulated amylase release from dispersed rat pancreatic acini. Higher concentration of the same drugs and diazepam (1 and 10 microM) which has high affinity for benzodiazepine receptors on gastrointestinal muscle, inhibited responses of ileum and gall-bladder to both CCK and acetylcholine.