Sources of Calcium in Neurokinin A–Induced Contractions of Human Colonic Smooth Musclein Vitro

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. Circular smooth muscle strips of human colon were suspended under 1 g of tension in organ baths containing Krebs solution at 37°C gased with 95% O2/5% CO2. Contractile activity was recorded isometrically. Cumulatively applied NKA (0.1 nmol/L–0.3 μmol/L), produced concentration-dependent contractions of human colonic smooth muscle strips that were not affected by tetrodotoxin (1 μmol/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 μmol/L), an L-type voltage-operated Ca2+ channel antagonist, abolished the contractile responses to NKA. Pretreatment with SK&F 96365 (10 μmol/L and 30 μmol/L), a putative receptor-activated and voltage-operated Ca2+ channel antagonist, attenuated the contractile responses. Depletion of intracellular Ca2+ stores with thapsigargin (1 μmol/L), an inhibitor of the sarcoplasmic reticulum Ca2+ ATP-ase, had no effect on NKA-induced contractions. 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.