title: Nicotine inhibits large conductance Ca(2+)-activated K(+) channels and the NO/-cGMP signaling pathway in cultured human endothelial cells.
abstract: OBJECTIVE
  The effects of nicotine on endothelium-dependent vasorelaxation mediated by nitric oxide (NO) are controversial. Since endothelial NO synthesis has been shown to depend on the activity of large conductance Ca(2 + )-activated K(+) channels (BK(Ca)), the present study investigated whether nicotine alters BK(Ca) single channel activity induced by the K(+) channel opener NS1619, and to examine a possible interaction with the endothelial NO generation.
  
  
  METHODS
  The patch-clamp technique was used to examine the BK(Ca) activity. NO production was measured indirectly using a [(3)H]-cGMP-radioimmunoassay. All experiments were performed using cultured endothelial cells derived from human umbilical cord veins.
  
  
  RESULTS
  The BK(Ca) opener NS1619 (10 micromol/l) significantly increased the BK(Ca) open-state probability (NPo) from 0.011+/-0.007 (control) to 0.052+/-0.019. Co-perfusion with nicotine (1 micromol/l) significantly decreased NS1619 induced NPo (n = 14, p < 0.05). Intracellular cGMP levels were significantly increased, if cells were stimulated with NS1619 (+ 225%; n = 10, p < 0.05), which was blocked by Nicotine (1 micromol/l).
  
  
  CONCLUSIONS
  The results of the present study demonstrate that BK(Ca) activation by NS1619 plays an important role in the regulation of the NO-/cGMP-signaling-pathway. Endothelial dysfunction caused by nicotine may be connected with a decrease in BK(Ca)-activity.
authors.affiliation: Department of Cardiology and Angiology, Justus-Liebig-University of Giessen, Klinikstrasse 36, Giessen 35392, Germany.
authors.forename: Christoph Rüdiger Wolfram
authors.initials: CR
authors.lastname: Kuhlmann
authors.forename: Jan Rasmus Friedrich Carl
authors.initials: JR
authors.lastname: Trümper
authors.forename: Harald
authors.initials: H
authors.lastname: Tillmanns
authors.forename: Christian
authors.initials: C
authors.lastname: Alexander Schaefer
authors.forename: Ali
authors.initials: A
authors.lastname: Erdogan
mesh_terms: D015220:Calcium Channels / Q000187:drug effects* / Q000502:physiology; D006152:Cyclic GMP; D004594:Electrophysiology; D042783:Endothelial Cells / Q000187:drug effects* / Q000502:physiology; D016232:Endothelins / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D009538:Nicotine / Q000009:adverse effects / Q000494:pharmacology*; D009569:Nitric Oxide; D015221:Potassium Channels / Q000187:drug effects* / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D015220:Calcium Channels; D016232:Endothelins; D015221:Potassium Channels; D009569:Nitric Oxide; D009538:Nicotine; D006152:Cyclic GMP