[3H]noradrenaline accumulation in cultured bovine adrenal medullary cells: modulation of accumulation by nicotine.
The mechanisms by which catecholamines are transported into adrenal medullary cells are not as well characterized as the high affinity catecholamine uptake system of sympathetic neurones. Therefore, we studied the accumulation of [3H]noradrenaline in 7-21 day old cultures of bovine adrenal cells. Cultured adrenal cells accumulate [3H]noradrenaline. The accumulation process has an apparent Km for noradrenaline of 0.47 mumol/l, is Na(+)-dependent, and is inhibited by desipramine, (-)-noradrenaline and (-)adrenaline (IC50's, 0.007, 0.9 and 3.8 mumol/l, respectively). Other aromatic amines also inhibit accumulation with an order of potency, (+)-amphetamine greater than or equal to dopamine greater than (-)-noradrenaline greater than (-)-adrenaline greater than or equal to 5-hydroxytryptamine. Nicotine and other stimulants of catecholamine release (acetylcholine and depolarizing K+ concentrations) were found to inhibit [3H]noradrenaline accumulation. Reserpine pretreatment (72 h) or omission of calcium did not prevent nicotine's inhibitory effect on accumulation, but did reduce or inhibit nicotine-induced catecholamine release, suggesting that adrenal [3H]noradrenaline accumulation may be regulated by processes involved with stimulus-secretion coupling (e.g., sodium gradient and/or depolarization) which are independent of release. These results suggest that the catecholamine transport mechanisms of cultured bovine adrenal cells and sympathetic neurones are similar and may be regulated by secretory processes.
McKay
D B
DB
Ohio State University, College of Pharmacy, Division of Pharmacology, Columbus 43210.
D000313:Adrenal Medulla / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D002395:Catecholamines / Q000378:metabolism; D002417:Cattle; D002478:Cells, Cultured; D003891:Desipramine / Q000494:pharmacology; D006584:Hexamethonium Compounds / Q000494:pharmacology; D009538:Nicotine / Q000378:metabolism* / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism*; D012110:Reserpine / Q000494:pharmacology; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000378:metabolism
D002395:Catecholamines; D006584:Hexamethonium Compounds; D009538:Nicotine; D012110:Reserpine; D003891:Desipramine; D009638:Norepinephrine