Sources of calcium in neurokinin A-induced contractions of human colonic smooth muscle in vitro.
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.
O'Riordan
A M
AM
Department of Veterinary Physiology and Biochemistry, Faculty of Veterinary Medicine, University College Dublin, Ireland.
Quinn
T
T
Hyland
J M
JM
O'Donoghue
D P
DP
Baird
A W
AW
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*
D015220:Calcium Channels; D015288:Neurokinin A; D002118:Calcium