EFFECTS OF CHRONIC NICOTINE ADMINISTRATION ON THE DENERVATED RAT ADRENAL MEDULLA

Abstract

The effects of chronic nicotine administration (1 or 10 mg/kg, s.c., twice daily) were studied in intact and denervated rat adrenal glands to determine the relative roles of central input and direct actions on catecholamines. Catecholamine depletion was obtained in the intact glands from 1–7 days of treatment with 10 mg/kg, with recovery by 14 days of treatment; catecholamines were not decreased in denervated adrenal glands. Catecholamine depletion was accompanied by a decline in functional storage vesicles (determined by [3H]‐adrenaline uptake per gland) in the intact side, while no change was seen in the denervated side; the proportion of newly synthesized vesicles increased markedly during 1–7 days of treatment with 10 mg/kg in the intact side, while a much smaller increase of shorter duration was seen in the denervated adrenal gland. Chronic nicotine administration at either dose level induced tyrosine hydroxylase in both intact and denervated glands, but the increase occurred more slowly in the denervated glands. Dopamine β‐hydroxylase levels increased similarly in both sides during treatment with nicotine (10 mg/kg). These studies suggest that although long‐term adrenal denervation eliminates the catecholamine depletion caused by chronic administration of nicotine, the mechanisms for induction of catecholamine synthesizing enzymes are still capable of responding to the drug. 1976 British Pharmacological Society