Effect of loxiglumide (CR 1505) on CCK-induced contractions and 3H-acetylcholine release from guinea-pig gallbladder.

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.

journal_name

Neuropeptides

journal_title

Neuropeptides

authors

Rakovska A,Sgaragli G,Mantovani P,Valoti M,Milenov K

doi

10.1016/0143-4179(93)90043-a

subject

Has Abstract

pub_date

1993-11-01 00:00:00

pages

271-6

issue

5

eissn

0143-4179

issn

1532-2785

pii

0143-4179(93)90043-A

journal_volume

25

pub_type

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