Calcium entry blockade as a mechanism for chlordimeform-induced inhibition of motor activity in the isolated guinea-pig ileum

S. M. Candura, P. Marraccini, L. G. Costa, L. Manzo, A. Rossi, T. Coccini, M. Tonini

Research output: Contribution to journalArticlepeer-review

Abstract

Central and peripheral α2-adrenoceptors, including those of the gastrointestinal tract, have been indicated as a toxicity target of formamidine pesticides in mammals. In this study, the inhibitory effect of chlordimeform on twitch contractions from electrically-stimulated longitudinal muscle-myenteric plexus preparations (LMMPs) of the guinea-pig ileum was found to be resistant to the action of the α2-adrenoceptor antagonist idazoxan. This drug was also ineffective on chlordimeform-induced inhibition of peristalsis recorded in whole ileal segments. As expected, idazoxan antagonized the inhibitory effect of the α2-adrenoceptor agonist clonidine on twitch contractions and peristaltic activity. Chlordimeform reduced the amplitude of direct mechanical responses to a variety of spasmogens such as acetylcholine, histamine and substance P, suggesting a muscular site of action. Moreover, in Ca2+-free, K+-depolarized LMPPs, chlordimeform inhibited submaximal contractions caused by addition of exogenous calcium, through an action apparently similar to that of the Ca2+ entry blocker nifedipine. Both chlordimeform- and nifedipine-induced inhibition of calcium contractions were reversed by the calcium channel activator BAY K 8644. This compound also partially prevented the inhibitory action of chlordimeform on peristaltic activity. On the whole, these results indicate that chlordimeform-induced depression of motor activity in the guinea-pig ileum is, at least in part, related to inhibition of transmembrane Ca2+ fluxes responsible for smooth muscle contraction.

Original languageEnglish
Pages (from-to)426-433
Number of pages8
JournalPharmacology and Toxicology
Volume71
Issue number6
Publication statusPublished - 1992

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology
  • Health, Toxicology and Mutagenesis

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