title: Sources of calcium in neurokinin A-induced contractions of human colonic smooth muscle in vitro.
abstract: OBJECTIVE
  Tachykinins have been implicated in the pathogenesis of colonic dysmotility. The sources of activator calcium for neurokinin A (NKA)-induced contraction of human colonic smooth muscle have not been assessed. We evaluated the contribution of extracellular and intracellular Ca2+ to NKA-induced contractions.
  
  
  METHODS
  Circular smooth muscle strips of human colon were suspended under 1 g of tension in organ baths containing Krebs solution at 37 degrees C gased with 95% O2/5% CO2. Contractile activity was recorded isometrically.
  
  
  RESULTS
  Cumulatively applied NKA (0.1 nmol/L-0.3 micromol/L), produced concentration-dependent contractions of human colonic smooth muscle strips that were not affected by tetrodotoxin (1 micromol/L). The contractile response to NKA was abolished in a Ca2+-free medium containing ethylenediaminetetraacetate (EDTA) (1 mmol/L). Pretreatment of muscle strips with nifedipine (1 micromol/L), an L-type voltage-operated Ca2+ channel antagonist, abolished the contractile responses to NKA. Pretreatment with SK&F 96365 (10 micromol/L and 30 micromol/L), a putative receptor-activated and voltage-operated Ca2+ channel antagonist, attenuated the contractile responses. Depletion of intracellular Ca2+ stores with thapsigargin (1 micromol/L), an inhibitor of the sarcoplasmic reticulum Ca2+ ATP-ase, had no effect on NKA-induced contractions.
  
  
  CONCLUSIONS
  NKA-mediated contraction of human colonic smooth muscle is dependent on an influx of extracellular Ca2+ through L-type voltage-operated Ca2+ channels. Intracellular Ca2+ release seems to have little role to play in NKA-mediated contractions.
authors.affiliation: Department of Veterinary Physiology and Biochemistry, Faculty of Veterinary Medicine, University College Dublin, Ireland.
authors.forename: A M
authors.initials: AM
authors.lastname: O'Riordan
authors.forename: T
authors.initials: T
authors.lastname: Quinn
authors.forename: J M
authors.initials: JM
authors.lastname: Hyland
authors.forename: D P
authors.initials: DP
authors.lastname: O'Donoghue
authors.forename: A W
authors.initials: AW
authors.lastname: Baird
mesh_terms: D002118:Calcium / Q000502:physiology*; D015220:Calcium Channels / Q000502:physiology*; D003106:Colon / Q000187:drug effects* / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology*; D015288:Neurokinin A / Q000494:pharmacology*
chemical_list: D015220:Calcium Channels; D015288:Neurokinin A; D002118:Calcium