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

OBJECTIVES: Tachykinins have been implicated in the pathogenesis of colonic dysmotility. The sources of activator calcium for neurokinin A (NKA)-induc ed contraction of human colonic smooth muscle have not been assessed. We ev aluated the contribution of extracellular and intracellular Ca2+ to NKA-ind uced contractions. METHODS: Circular smooth muscle strips of human colon were suspended under 1 g of tension in organ baths containing Krebs solution at 37 degreesC gase d with 95% O-2/5% CO2. Contractile activity was recorded isometrically. RESULTS: Cumulatively applied NKA (0.1 nmol/L-0.3 mu mol/L), produced conce ntration-dependent contractions of human colonic smooth muscle strips that were not affected by tetrodotoxin (1 mu mol/L). The contractile response to NKA was abolished in a Ca2+-free medium containing ethylenediaminetetraace tate (EDTA) (1 mmol/L). Pretreatment of muscle strips with nifedipine (1 mu mol/L), an L-type voltage-operated Ca2+ channel antagonist, abolished the contractile responses to NKA. Pretreatment with SK&F 96365 (10 mu mol/L and 30 mu mol/L), a putative receptor-activated and voltage-operated Ca2+ chan nel antagonist, attenuated the contractile responses. Depletion of intracel lular Ca2+ stores with thapsigargin (1 mu mol/L), an inhibitor of the sarco plasmic reticulum Ca2+ ATP-ase, had no effect on NKA-induced contractions. CONCLUSIONS: NKA-mediated contraction of human colonic smooth muscle is dep endent on an influx of extracellular Ca2+ through L-type voltage-operated C a2+ channels. Intracellular Ca2+ release seems to have little role to play in NKA-mediated contractions. (C) 2001 by Am. Coll. of Gastroenterology.