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ROLE OF EXTRACELLULAR CALCIUM IN THE EFFECTS OF SUBSTANCE P AND NEUROKININ A ON GUINEA PIG TRACHEA AND HUMAN BRONCHUS
Author(s) -
MATRAN R.,
NALINE E.,
ADVENIER C.,
LOCKHART A.,
TRICOT J.F.,
REGOLI D.
Publication year - 1988
Publication title -
fundamental and clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.655
H-Index - 73
eISSN - 1472-8206
pISSN - 0767-3981
DOI - 10.1111/j.1472-8206.1988.tb00620.x
Subject(s) - neurokinin a , substance p , tetraethylammonium , calcium , histamine , verapamil , acetylcholine , chemistry , endocrinology , medicine , tetraethylammonium chloride , potassium , biology , biochemistry , neuropeptide , receptor , organic chemistry
Summary— Whether the influux of calcium through voltage‐operated channels is involved in the stimulatory effects of substance P and neurokinin A in aiways smooth muscle is not yet firmly established. This question was addressed in the present study using guinea pig trachea and human bronchi suspended in normal or calcium‐free Krebs solution and tested with inhibitors of calcium channels. In calcium‐free Krebs solution, the myotropic effects of substance P (10 −7 M), neurokinin A (3.10 −8 M), acetylcholine (2.10 −5 M), and histamine (2.10 −5 M) were reduced by 27–57%, while those of potassium chloride and tetraethylammonium were practically abolished. Calcium antagonists such as verapamil or nicardipine, when applied at concentrations of 10 −8 ‐10 −6 M, inhibited the contractions produced by potassium chloride and tetraethylammonium, whereas higher concentrations (10 −5 ‐10 −4 M) of both inhibitors were needed to reduce the effects of substance P, neurokinin A, acetylcholine, and histamine. In neither preparation did the calcium agonist Bay K 8644 (10 −6 M) modify the effects of neurokinin A, substance P, acetylcholine, or histamine, but it potentiated potassium chloride's effect on human bronchi. We conclude that transmembrane calcium influx through voltage‐operated channels plays a minor role in the stimulatory effects of neurokinins in airways smooth muscle.