Abstract
Substance P and related tachykinins are present in the mammalian gut and act as neurotransmitters. Microfluorimetric measurement of intracellular calcium ([Ca2+]i) was used to study tachykinin-sensitive myenteric neurons. Substance P (0.001-10 microM) evoked concentration-dependent increases in percentage of neurons responding (6-75%) and delta [Ca2+]i (88 +/- 24 to 212 +/- 16 nM). Neurokinin A (0.001-1 microM) produced similar responses. Removal of extracellular Ca2+ abolished substance P-induced Ca2+ signals, as did the addition of the Ca2+ channel blockers lanthanum chloride (5 mM) and nickel chloride (2.5 mM). Both nifedipine (1-50 microM) and diltiazem (1-50 microM) inhibited substance P-evoked Ca2+ responses in a dose-dependent manner. Substance P and related tachykinins evoke Ca2+ signaling in cultured myenteric neurons by the influx of extracellular Ca2+ through L and N-type plasma membrane Ca2+ channels.
MeSH terms
-
Animals
-
Calcium / metabolism*
-
Calcium Channel Blockers / pharmacology
-
Calcium Channels / metabolism
-
Cells, Cultured
-
Diltiazem / pharmacology
-
Dipeptides / pharmacology
-
Fluorometry
-
Guinea Pigs
-
Indoles / pharmacology
-
Lanthanum / pharmacology
-
Myenteric Plexus / drug effects*
-
Myenteric Plexus / metabolism
-
Neurokinin A / pharmacology
-
Nickel / pharmacology
-
Nifedipine / pharmacology
-
Peptide Fragments / pharmacology
-
Peptides, Cyclic / pharmacology
-
Receptors, Tachykinin / agonists
-
Receptors, Tachykinin / classification
-
Substance P / analogs & derivatives
-
Substance P / pharmacology*
-
Tachykinins / pharmacology*
-
Virulence Factors, Bordetella / pharmacology
Substances
-
Calcium Channel Blockers
-
Calcium Channels
-
Dipeptides
-
Indoles
-
Peptide Fragments
-
Peptides, Cyclic
-
Receptors, Tachykinin
-
Tachykinins
-
Virulence Factors, Bordetella
-
senktide
-
cyclo(Gln-Trp-Phe-Gly-Leu-Met)
-
FK 888
-
Substance P
-
Lanthanum
-
Nickel
-
Neurokinin A
-
Diltiazem
-
Nifedipine
-
Calcium