title: A pyridinium derivative from Red Sea soft corals inhibited voltage-activated potassium conductances and increased excitability of rat cultured sensory neurones.
abstract: BACKGROUND
  Whole cell patch clamp recording and intracellular Ca2+ imaging were carried out on rat cultured dorsal root ganglion (DRG) neurones to characterize the actions of crude extracts and purified samples from Red Sea soft corals. The aim of the project was to identify compounds that would alter the excitability of DRG neurones.
  
  
  RESULTS
  Crude extracts of Sarcophyton glaucum and Lobophyton crassum attenuated spike frequency adaptation causing DRG neurones to switch from firing single action potentials to multiple firing. The increase in excitability was associated with enhanced KCl-evoked Ca2+ influx. The mechanism of action of the natural products in the samples from the soft corals involved inhibition of voltage-activated K+ currents. An active component of the crude marine samples was identified as 3-carboxy-1-methyl pyridinium (trigonelline). Application of synthetic 3-carboxy-1-methyl pyridinium at high concentration (0.1 mM) also induced multiple firing and reduced voltage-activated K+ current. The changes in excitability of DRG neurones induced by 3-carboxy-1-methyl pyridinium suggest that this compound contributes to the bioactivity produced by the crude extracts from two soft corals.
  
  
  CONCLUSIONS
  Sarcophyton glaucum and Lobophyton crassum contain natural products including 3-carboxy-1-methyl pyridinium that increase the excitability of DRG neurones. We speculate that in addition to developmental control and osmoregulation these compounds may contribute to chemical defenses.
authors.affiliation: Marine Science Department, Suez Canal University, Ismailia, Egypt. ttemraz@yahoo.com
authors.forename: Tarek A
authors.initials: TA
authors.lastname: Temraz
authors.forename: Wael E
authors.initials: WE
authors.lastname: Houssen
authors.forename: Marcel
authors.initials: M
authors.lastname: Jaspars
authors.forename: David R
authors.initials: DR
authors.lastname: Woolley
authors.forename: Kerrie N
authors.initials: KN
authors.lastname: Wease
authors.forename: Steven N
authors.initials: SN
authors.lastname: Davies
authors.forename: Roderick H
authors.initials: RH
authors.lastname: Scott
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D037421:Anthozoa; D002478:Cells, Cultured; D005727:Ganglia, Spinal / Q000187:drug effects / Q000502:physiology; D019156:Indian Ocean; D009433:Neural Inhibition / Q000187:drug effects* / Q000502:physiology; D009475:Neurons, Afferent / Q000187:drug effects* / Q000502:physiology; D026902:Potassium Channel Blockers / Q000302:isolation & purification / Q000494:pharmacology*; D024642:Potassium Channels, Voltage-Gated / Q000037:antagonists & inhibitors* / Q000502:physiology; D011726:Pyridinium Compounds / Q000302:isolation & purification / Q000494:pharmacology*; D051381:Rats
chemical_list: D026902:Potassium Channel Blockers; D024642:Potassium Channels, Voltage-Gated; D011726:Pyridinium Compounds