Thapsigargin blocks the mobilisation of intracellular calcium caused by activation of human NK1 (long) receptors expressed in Chinese hamster ovary cells.
Neurokinin receptors can couple to several second messenger systems including phospholipase C and intracellular calcium mobilisation. Using FURA-2 microspectrofluorimetry, this study examines the mobilisation of calcium in CHO cells which had been stably transfected with the long isoform of the human NK1 receptor. Substance P caused a concentration-dependent rise in inositol phosphate production which was correlated with a reversible increase in intracellular calcium levels. The mobilisation of calcium was reduced by the removal of extracellular calcium from the bathing solution, and almost totally abolished by depletion of intracellular calcium pools with 1 microM thapsigargin. These data suggest that the transduction mechanism associated with NK1 (long) receptor activation can utilise both intracellular and extracellular calcium pools in this expression system.
Seabrook
G R
GR
Merck Sharp & Dohme Research Laboratories, Neuroscience Research Centre, Terlings Park, Harlow, Essex, UK.
Fong
T M
TM
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D016466:CHO Cells / Q000187:drug effects / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D006224:Cricetinae; D003412:Cricetulus; D006801:Humans; D007295:Inositol Phosphates / Q000378:metabolism; D017981:Receptors, Neurotransmitter / Q000187:drug effects* / Q000235:genetics; D018039:Receptors, Tachykinin; D011994:Recombinant Proteins / Q000378:metabolism; D015290:Second Messenger Systems / Q000187:drug effects*; D013373:Substance P / Q000031:analogs & derivatives / Q000494:pharmacology; D013729:Terpenes / Q000494:pharmacology*; D019284:Thapsigargin; D014162:Transfection
D007295:Inositol Phosphates; D017981:Receptors, Neurotransmitter; D018039:Receptors, Tachykinin; D011994:Recombinant Proteins; D013729:Terpenes; D013373:Substance P; D019284:Thapsigargin; D002118:Calcium