Role of extracellular calcium in the effects of substance P and neurokinin A on guinea pig trachea and human bronchus.
Whether the influx of calcium through voltage-operated channels is involved in the stimulatory effects of substance P and neurokinin A in airways 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.
D000818:Animals; D001980:Bronchi / Q000187:drug effects*; D002118:Calcium / Q000494:pharmacology*; D006168:Guinea Pigs; D006801:Humans; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D015288:Neurokinin A; D009479:Neuropeptides / Q000494:pharmacology*; D009529:Nicardipine / Q000494:pharmacology; D013373:Substance P / Q000494:pharmacology*; D013806:Theophylline / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects*; D014700:Verapamil / Q000494:pharmacology
D009479:Neuropeptides; D013373:Substance P; D015288:Neurokinin A; D013806:Theophylline; D014700:Verapamil; D009529:Nicardipine; D007545:Isoproterenol; D002118:Calcium