Release of [3H]-acetylcholine (3H-ACh) and muscle contractions in response to cholecystokinin (CCK) were measured and recorded simultaneously from isolated guinea-pig gallbladder. Cholecystokinin octapeptide (CCK8) (10(-10)-10(-7) M) enhanced the release of [3H]ACh and the contractions of the muscle. TTX (10(-6) M) inhibited the CCK-induced release of 3H-ACh by only 30%. In Ca(2+)-free medium CCK8 had no effect. Loxiglumide, (CR 1505), a newly synthesized nonpeptide CCK-A-receptor antagonist, D.L-(3,4-dichlorbenzoilamino)-5-/N-(3-methoxypropyl)-pentylamin o-5-oxo-pentanoi c acid, antagonized both the ACh-releasing effect of CCK and the contractions in a dose-dependent manner. The affinity (pA2) of CR 1505 to CCK-receptors, determined by the shift of the concentration-response curves for CCK8 was 8.36. It was 5 logarithmic orders higher than the pA2 of proglumide. The IC50 value of CR 1505 calculated by the CCK-induced release of 3H-ACh was 10 nM. The results suggest the existence not only of muscular CCK receptors but also neuronal receptors for CCK probably located on cholinergic nerves.
Rakovska, A., Sgaragli, G.P., Mantovani, P., Valoti, M., Milenov, K. (1993). Effect of loxiglumide (CR 1505) on CCK-induced contractions and 3H-acetylcholine release from guinea-pig gallbladder. NEUROPEPTIDES, 25(5), 271-276 [10.1016/0143-4179(93)90043-A].
Effect of loxiglumide (CR 1505) on CCK-induced contractions and 3H-acetylcholine release from guinea-pig gallbladder
Sgaragli, G. P.;Mantovani, Piero;Valoti, Massimo;
1993-01-01
Abstract
Release of [3H]-acetylcholine (3H-ACh) and muscle contractions in response to cholecystokinin (CCK) were measured and recorded simultaneously from isolated guinea-pig gallbladder. Cholecystokinin octapeptide (CCK8) (10(-10)-10(-7) M) enhanced the release of [3H]ACh and the contractions of the muscle. TTX (10(-6) M) inhibited the CCK-induced release of 3H-ACh by only 30%. In Ca(2+)-free medium CCK8 had no effect. Loxiglumide, (CR 1505), a newly synthesized nonpeptide CCK-A-receptor antagonist, D.L-(3,4-dichlorbenzoilamino)-5-/N-(3-methoxypropyl)-pentylamin o-5-oxo-pentanoi c acid, antagonized both the ACh-releasing effect of CCK and the contractions in a dose-dependent manner. The affinity (pA2) of CR 1505 to CCK-receptors, determined by the shift of the concentration-response curves for CCK8 was 8.36. It was 5 logarithmic orders higher than the pA2 of proglumide. The IC50 value of CR 1505 calculated by the CCK-induced release of 3H-ACh was 10 nM. The results suggest the existence not only of muscular CCK receptors but also neuronal receptors for CCK probably located on cholinergic nerves.
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https://hdl.handle.net/11365/38808
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