Evaluation of a new and potent cholecystokinin antagonist on motor responses of the guinea-pig intestine

L. Barthó, P. Holzer, F. Lembeck, I. T. Lippe, I. Setnikar

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

1 The potency and selectivity of D,L-4-(3,4-dichloro-benzoyl-amino)-5-(dipentyl-amino)-5-oxo-pentanoic acid (CR 1409) as a cholecystokinin (CCK) antagonist was investigated on motor responses of the longitudinal and circular muscles of the guinea-pig isolated ileum. CR 1409 was further used to examine whether nerve-mediated motor responses to electrical field stimulation or distension of the gut wall may involve the release of CCK-like peptides. 2 CR 1409 (0.06-2.1 μM) antagonized longitudinal muscle responses to ceruletide (caerulein, a CCK-related decapeptide) in a concentration dependent and competitive manner (pA2 7.77); responses to CCK-octapeptide (CCK-8) were antagonized with a similar potency. Contractions of the circular muscle evoked by ceruletide were also blocked by CR 1409 (0.2-0.4 μM). 3 Longitudinal muscle contractions in response to dimethylphenylpiperazinium, bethanechol, histamine, substance P, or 5-hydroxytryptamine (5-HT), and circular muscle contractions evoked by acetylcholine, 5-HT, substance P, or substance K were not altered by CR 1409 (0.4 μM). Longitudinal muscle contractions induced by electrical field stimulation (with pulses delivered at 0.05 and 1 Hz in the absence, and at 5 Hz in the presence of atropine) were not or only slightly reduced by CR 1409 (0.4 μM). Longitudinal contractions due to activation of extrinsic nerves by capsaicin remained unaltered in the presence of CR 1409 (0.4 μM). 4 Reflex contractions of the circular muscle, induced by balloon distension and recorded orally to the site of distension, and peristaltic activity elicited by intraluminal infusion of Tyrode solution remained unaffected by CR 1409 (0.4 μM). 5 These findings indicate that CR 1409 is a potent and selective antagonist of CCK-like peptides in the guinea-pig ileum. The results do not provide any evidence that CCK-like peptides, released from extrinsic or intrinsic neurones, are involved in nerve-mediated contractions of intestinal muscle and in the peristaltic reflex.

Original languageEnglish
Pages (from-to)753-761
Number of pages9
JournalBritish Journal of Pharmacology
Volume90
Issue number4
Publication statusPublished - 1987

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Cholecystokinin
Intestines
Guinea Pigs
Muscle Contraction
Ceruletide
Substance P
Ileum
Peptides
Electric Stimulation
Reflex
Serotonin
Pentanoic Acids
Dimethylphenylpiperazinium Iodide
Bethanechol
Neurokinin A
Keto Acids
lorglumide
Sincalide
Muscles
Capsaicin

ASJC Scopus subject areas

  • Pharmacology

Cite this

Evaluation of a new and potent cholecystokinin antagonist on motor responses of the guinea-pig intestine. / Barthó, L.; Holzer, P.; Lembeck, F.; Lippe, I. T.; Setnikar, I.

In: British Journal of Pharmacology, Vol. 90, No. 4, 1987, p. 753-761.

Research output: Contribution to journalArticle

Barthó, L. ; Holzer, P. ; Lembeck, F. ; Lippe, I. T. ; Setnikar, I. / Evaluation of a new and potent cholecystokinin antagonist on motor responses of the guinea-pig intestine. In: British Journal of Pharmacology. 1987 ; Vol. 90, No. 4. pp. 753-761.
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