Cholecystokinin antagonism by benzodiazepines in the contractile response of the isolated guinea-pig gallbladder

β-Carbolines Selectively Antagonize the Cholecystokinin Action in Isolated Guinea-Pig Gallbladder Muscle

“…In the experiments showing the parallel shift of the CCK dose-response curve by Q-carbolines, we added a low concentration of atropine to the Locke-Ringer solution in order to block the contractile effect of endogenous ACh that would be released by CCK from the cholinergic neurons (20)(21)(22). This procedure also implied that in the parallel shift experi ments, the receptors involved in the CCK response are those on the smooth muscle cell membrane and excludes those on the neurons, although the contribution of the neuronal CCK receptors is essentially a minor one in the CCK-induced contraction of the guinea pig gallbladder as compared with those on the smooth muscle cells according to the previous paper (2).…”

“…On the basis of the pA2 values, (3-CCM is stronger as a CCK antagonist than Q-CCE, but a little weaker than diazepam (2).…”

“…Later, they showed that the antagonism could be observed not only in the contractile response of the guinea-pig gallbladder muscle (2) but also in the various central effects induced by CCK (3,4), and the antagonism probably took place at the CCK receptor sites, at least in the gallbladder, because BZP caused the parallel shift of the dose-response curve for CCK (2). In addition, we also showed (5) that BZP could protect CCK receptors from alkylation by dibenamine, which has been used as a receptor alkylating agent (6,7), while Bradwejn and De Montigny (1984) (8) electrophysiologically demonstrated the BZP-CCK antagonism in rat hippocampal neurons.…”

Inhibition of Hypothermic Effect of Cholecystokinin by Benzodiazepines and a Benzodiazepine Antagonist, Ro 15-1788, in Mice

“…We found that 10-6 to 10-5 M of CDP and DZP competitively antagonized the CCK8 action of contracting the isolated guinea-pig gallbladder muscle (12,13). On the other hand, the intraperitoneal doses of the benzodiazepines required for reversing CCK8 hypothermia and antinociception (5) were as low as 0.5 to 2 mg/kg.…”

Benzodiazepine/cholecystokinin interactions at functional CCK receptors in rat brain

“…The first is the profound CCK receptor desensitization which is seen in hippocampal slice preparations (Dodd & Kelly, 1981;Boden & Hill, 1988b). Secondly, in vitro studies on the CCK response in hippocampus suggests a CCKB receptor on CAl hippocampal neurones (Dodd & Kelly, 1981;Boden & Hill, 1988b), which is in stark contrast to the lack of efficacy of the non-sulphated octapeptide of CCK reported by Bradwejn & (Kubota et al, 1985b).…”