Natural Compounds Endowed with Cholinergic or Anticholinergic Activity. Enhancement of Acetylcholine Release by a Quaternary Derivative of l-Hyoscyamine

Natural Compounds Endowed with Cholinergic or Anticholinergic Activity. Enhancement of Acetylcholine Release by a Quaternary Derivative of l-Hyoscyamine

Author Souccar, Caden Google Scholar
Salamanca, Ana Lucia V. Google Scholar
Tanae, Mirtes M. Google Scholar
Lima-Landman, Maria Teresa R. Google Scholar
Lapa, Antonio José Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Abstract New compounds that target nicotinic receptors (nAChRs) have been sought to correct disorders affecting cholinergic transmission in central and peripheral synapses. A quaternary derivate of l-hyoscyamine, phenthonium (Phen), was shown by our group to enhance the spontaneous acetylcholine (ACh) release without altering the nerve-induced transmitter release at the neuromuscular junction. the effect was unrelated to membrane depolarization, and was not induced by an increase of calcium influx into the nerve terminal. Phen also presented a competitive antimuscarinic activity and blocked noncompetitively the neuromuscular transmission. in this work we re-examined the mechanisms underlying the facilitatory actions of Phen on [(3)H]-ACh release in isolated ganglia of the guinea pig ileal myenteric plexus. Exposure of the preparations to Phen (10-50 mu M) increased the release of [(3)H]-ACh by 81 to 68% over the basal. the effect was not affected by the ganglionic nAChR antagonist hexamethonium (1 nM) at a concentration that inhibited the increase of [(3)H]-ACh release induced by the nicotinic agonist dimethylphenylpiperazinium (DMPP, 30 mu M). Association of Phen (10 mu M) with DMPP potentiated the facilitatory effect of Phen. [(3)H]-ACh release was not altered by the muscarinic antagonists atropine (1 nM) or pirenzepine (1 mu M). However, both antagonists inhibited the release of [(3)H]-ACh induced by either the muscarinic M1 agonist McN-343 (10 mu M) or Phen (20 mu M). the facilitatory effect of Phen was not altered by CdCl(2) (50 mM), but it was potentiated in the presence of tetraethylammonium (40 mM). the results indicate that the facilitatory action of Phen appears to be mediated by an increase of the inwardly rectifying potassium channels conductance probably related to the compound antimuscarinic activity.
Keywords Natural products
Acetylcholine release
Anticholinergic activity
L-Hyoscyamine
Potassium channels
Language English
Date 2010-01-01
Published in Journal of Molecular Neuroscience. Totowa: Humana Press Inc, v. 40, n. 1-2, p. 138-142, 2010.
ISSN 0895-8696 (Sherpa/Romeo, impact factor)
Publisher Humana Press Inc
Extent 138-142
Origin http://dx.doi.org/10.1007/s12031-009-9228-1
Access rights Closed access
Type Article
Web of Science ID WOS:000273753500021
URI http://repositorio.unifesp.br/handle/11600/32080

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