title: Effect of substance P and its precursor alpha-protachykinin on intracellular free calcium concentration in human polymorphonuclear leukocytes.
abstract: The increase in intracellular free calcium concentration is an important step in signal transduction leading to phagocyte activation. The undecapeptide substance P can influence various functions of human polymorphonuclear leukocytes, including chemotaxis, phagocytosis, and respiratory burst. In this study we investigated the ability of low-concentration (that can occur in vivo) substance P (10(-7) M) and its precursor alpha-protachykinin (3 x 10(-7) M) to increase the intracellular free calcium concentration in human polymorphonuclear leukocytes. Cells isolated from ten healthy donors were incubated with substance P or alpha-protachykinin in 1 mM calcium medium for 5 min and the intracellular free calcium concentration was monitored using the fluorescent calcium indicator Fura-2am. Polymorphonuclear leukocytes from 40% of donors responded to both agonists. The substance P- and alpha-protachykinin-induced increase in intracellular free calcium concentration was 59 +/- 13 nM and 58 +/- 12 nM and the extracellular calcium influx contributed to 87 +/- 8% and 54 +/- 8% of the calcium response, respectively. alpha-Protachykinin released almost all the calcium from intracellular stores, while substance P mobilized only 24 +/- 5% of this calcium pool. Finally, cells that responded to a single challenge with substance P and alpha-protachykinin were able to increase their intracellular free calcium concentration in response to each of three consecutive stimulations with these agonists. This may be an additional mechanism by which substance P and its precursor modify the function of human polymorphonuclear leukocytes.
authors.affiliation: Department of Pneumology and Allergology, Medical University of Lodz, Poland.
authors.forename: D
authors.initials: D
authors.lastname: Nowak
authors.forename: E
authors.initials: E
authors.lastname: Hrabec
authors.forename: J
authors.initials: J
authors.lastname: Greger
authors.forename: G
authors.initials: G
authors.lastname: Piasecka
authors.forename: M
authors.initials: M
authors.lastname: Krol
authors.forename: P
authors.initials: P
authors.lastname: Bialasiewicz
authors.forename: A
authors.initials: A
authors.lastname: Antczak
authors.forename: G
authors.initials: G
authors.lastname: Plucienniczak
authors.forename: A
authors.initials: A
authors.lastname: Plucienniczak
mesh_terms: D002118:Calcium / Q000097:blood*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D011498:Protein Precursors / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000494:pharmacology; D012016:Reference Values; D013373:Substance P / Q000494:pharmacology*; D015320:Tachykinins / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D007211:Indoles; D011498:Protein Precursors; D011994:Recombinant Proteins; D015320:Tachykinins; C054618:protachykinin; D013373:Substance P; D009240:N-Formylmethionine Leucyl-Phenylalanine; D000252:Calcium-Transporting ATPases; D002118:Calcium; C000543:cyclopiazonic acid