Capsaicin inhibits catecholamine secretion and synthesis by blocking Na+ and Ca2+ influx through a vanilloid receptor-independent pathway in bovine adrenal medullary cells.
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.
Takahashi
Kojiro
K
Department of Hospital Pharmacy, University of Occupational and Environmental Health, Kitakyushu, Japan.
Toyohira
Yumiko
Y
Ueno
Susumu
S
Tsutsui
Masato
M
Yanagihara
Nobuyuki
N
D000313:Adrenal Medulla / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology; D000818:Animals; D001547:Benzaldehydes / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002132:Calcium Radioisotopes; D002211:Capsaicin / Q000031:analogs & derivatives / Q000494:pharmacology*; D002217:Carbachol / Q000494:pharmacology; D002395:Catecholamines / Q000096:biosynthesis* / Q000378:metabolism; D002417:Cattle; D002478:Cells, Cultured; D018679:Cholinergic Agonists / Q000494:pharmacology; D004295:Dihydroxyphenylalanine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006632:Histamine / Q000494:pharmacology; D017136:Ion Transport / Q000187:drug effects; D012430:Ruthenium Red / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D012964:Sodium / Q000378:metabolism*; D012979:Sodium Radioisotopes; D050916:TRPV Cation Channels / Q000502:physiology*; D014446:Tyrosine 3-Monooxygenase / Q000037:antagonists & inhibitors / Q000378:metabolism; D014701:Veratridine / Q000494:pharmacology
D018712:Analgesics, Non-Narcotic; D001547:Benzaldehydes; D002132:Calcium Radioisotopes; D002395:Catecholamines; D018679:Cholinergic Agonists; D012979:Sodium Radioisotopes; D050916:TRPV Cation Channels; D012430:Ruthenium Red; D004295:Dihydroxyphenylalanine; D014701:Veratridine; D006632:Histamine; D002217:Carbachol; D012964:Sodium; C100058:vanillin; D014446:Tyrosine 3-Monooxygenase; C071423:capsazepine; D002211:Capsaicin; D002118:Calcium