Sources of calcium in neurokinin A-induced contractions of human colonic smooth muscle in vitro

Am J Gastroenterol. 2001 Nov;96(11):3117-21. doi: 10.1111/j.1572-0241.2001.05257.x.

Abstract

Objectives: 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.

MeSH terms

  • Calcium / physiology*
  • Calcium Channels / physiology*
  • Colon / drug effects*
  • Colon / physiology*
  • Humans
  • In Vitro Techniques
  • Muscle Contraction / drug effects*
  • Muscle, Smooth / drug effects*
  • Muscle, Smooth / physiology*
  • Neurokinin A / pharmacology*

Substances

  • Calcium Channels
  • Neurokinin A
  • Calcium