Further biological activities of the novel choline analogs selenonium choline and acetylselenonium choline

A. V. Terry, L. A. Silks, R. B. Dunlap, J. D. Odom, J. W. Kosh

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

The pharmacological actions of the novel choline analog, selenonium choline [(CH3)2Se+CH2CH2OH] and its acetyl ester acetylselenonium choline (ASeCh) were studied in vivo and in vitro. ASeCh produced a dose- related decrease in mean arterial pressure in the rat similar to acetylcholine (ACh) but was 1% to 2% as potent. ASeCh demonstrated agonist activity on the rat isolated ileum and was approximately 2% as active as ACh. Selenonium chlorine (SeCh) was taken up and acetylated in brain tissue slices in a time- and concentration-dependent manner. The use of KCl as a loading stimulus did not increase the uptake of SeCh but increased tissue levels of ASeCh 1.5-fold over the control concentrations. The uptake of SeCh was described by a single low-affinity uptake component (K(m) = 167 μM) that was not blocked by hemicholinium-3. In contrast, hemicholinium significantly blocked the acetylation of SeCh. Compared with basal release, depolarization with KCl caused a significant release of ASeCh into the incubation medium. A neural specificity was suggested for the in vitro uptake of SeCh. Acetylation of SeCh in vivo in the rat after intraventricular administration was similar to the extent of acetylation of [2H4]-choline. ASeCh bound to both M1 and M2 cholinergic receptors with 2% to 3% of the affinity observed for ACh. These data suggest that SeCh may satisfy criteria for a false neurotransmitter precursor.

Original languageEnglish (US)
Pages (from-to)593-601
Number of pages9
JournalJournal of Pharmacology and Experimental Therapeutics
Volume266
Issue number2
StatePublished - Jan 1 1993
Externally publishedYes

    Fingerprint

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

Cite this