Inhibitory effects of propofol on catecholamine secretion and uptake in cultured bovine adrenal medullary cells.
In the central and peripheral noradrenergic neurons, the balance between noradrenaline release and reuptake determines the level of noradrenaline at the synaptic cleft or the nerve ending. In the present study, we examined the effects of propofol, an intravenous general anaesthetic, on catecholamine secretion and noradrenaline uptake in cultured bovine adrenal medullary cells and on the serum noradrenaline and blood pressure in rats. In cultured adrenal medullary cells, propofol (10-50 mumol/l) concentration-dependently inhibited catecholamine secretion stimulated by carbachol. Propofol suppressed carbachol-evoked 22Na+ influx as well as 45Ca2+ influx at concentrations similar to those which suppressed the catecholamine secretion. Propofol (10-50 mumol/l) also inhibited veratridine-evoked 22Na+ influx, 45Ca2+ influx and catecholamine secretion, whereas it had little effect on the 45Ca2+ influx and catecholamine secretion induced by 56 mmol/l K+. Cultured adrenal medullary cells show [3H] noradrenaline uptake which is sensitive to imipramine. Propofol (10-50 mumol/l) significantly inhibited the imipramine-sensitive uptake of [3H] noradrenaline. In rats, intravenous administration of propofol (2.5 mg/kg) lowered serum noradrenaline and arterial blood pressure. From these findings, in spite of inhibiting noradrenaline uptake, propofol at anaesthetic concentrations (10-30 mumol/l) seems to reduce catecholamine secretion by interfering with Na+ influx through voltage-dependent Na+ channels as well as nicotinic acetylcholine receptor-associated ion channels in the adrenal medulla and, probably, in the sympathetic nervous system. This may explain the propofol-induced hypotension during anaesthesia.
Minami
K
K
Department of Anaesthesiology, University of Occupational and Environmental Health, School of Medicine, Kitakyushu, Japan.
Yanagihara
N
N
Segawa
K
K
Tsutsui
M
M
Shigematsu
A
A
Izumi
F
F
D000313:Adrenal Medulla / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018686:Anesthetics, Intravenous / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002217:Carbachol / Q000494:pharmacology; D002417:Cattle; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D007022:Hypotension / Q000139:chemically induced; D008297:Male; D018722:Nicotinic Agonists / Q000494:pharmacology; D009638:Norepinephrine / Q000097:blood / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism; D015742:Propofol / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000378:metabolism; D014701:Veratridine / Q000494:pharmacology
D018686:Anesthetics, Intravenous; D018722:Nicotinic Agonists; D014701:Veratridine; D002217:Carbachol; D012964:Sodium; D011188:Potassium; D002118:Calcium; D009638:Norepinephrine; D015742:Propofol