capsazepine and vanillin

We report here the effects of capsaicin, a flavoring ingredient in the hot pepper Capsicum family, on catecholamine secretion and synthesis in cultured bovine adrenal medullary cells. Capsaicin inhibited catecholamine secretion (IC(50)=9.5, 11.8, and 62 microM) stimulated by carbachol, an agonist of the nicotinic acetylcholine receptor, by veratridine, an activator of voltage-dependent Na(+) channels, and by high K(+), an activator of voltage-dependent Ca(2+) channels, respectively. Capsaicin also suppressed carbachol-induced (22)Na(+) influx (IC(50)=5.0 microM) and (45)Ca(2+) influx (IC(50)=24.4 muM), veratridine-induced (22)Na(+) influx (IC(50)=2.4 microM) and (45)Ca(2+) influx (IC(50)=1.1 microM), and high K(+)-induced (45)Ca(2+) influx (IC(50)=5.8 microM). The reduction in catecholamine secretion caused by capsaicin was not overcome by increasing the concentration of carbachol. Furthermore, capsazepine (10 microM), a competitive antagonist for the transient receptor potential vanilloid 1, and ruthenium red (30 microM), a nonselective cation channel antagonist, did not block the inhibition by capsaicin of catecholamine secretion. Capsaicin also suppressed both basal and carbachol-stimulated (14)C-catecholamine synthesis (IC(50)=10.6 and 26.4 microM, respectively) from [(14)C] tyrosine but not from L: -3, 4-dihydroxyphenyl [3-(14)C] alanine ([(14)C] DOPA) as well as tyrosine hydroxylase activity (IC(50)=8.4 and 39.0 microM, respectively). The present findings suggest that capsaicin inhibits catecholamine secretion and synthesis via suppression of Na(+) and Ca(2+) influx through a vanilloid receptor-independent pathway.

Topics: Adrenal Medulla; Analgesics, Non-Narcotic; Animals; Benzaldehydes; Calcium; Calcium Radioisotopes; Capsaicin; Carbachol; Catecholamines; Cattle; Cells, Cultured; Cholinergic Agonists; Dihydroxyphenylalanine; Dose-Response Relationship, Drug; Histamine; Ion Transport; Ruthenium Red; Signal Transduction; Sodium; Sodium Radioisotopes; TRPV Cation Channels; Tyrosine 3-Monooxygenase; Veratridine