Nicotine tolerance in chromaffin cell cultures: acute and chronic exposure to smoking-related nicotine doses.
Nicotine tolerance and dependence are key aspects of tobacco addiction; however, the cellular mechanisms underlying these phenomena are poorly understood. Adrenal chromaffin cells release catecholamines upon exposure to nicotine and with repeated exposure this response exhibits nicotine tolerance. Using bovine adrenal chromaffin cells in culture, we have demonstrated acute and chronic nicotine tolerance at doses relevant to that in the blood and tissues of smokers (10(-7) M to 10(-6) M). Chromaffin cells are preexposed to low doses of nicotine for time periods ranging from 10 min to 7 days and then subsequently challenged with a maximally stimulating dose of nicotine (10(-5) M) for 10 min, all at 37 degrees C. Preexposure to nicotine results in a depression of 45Ca uptake and catecholamine release upon subsequent nicotine challenge. Acute tolerance or desensitization of nicotine-stimulated catecholamine release begins to occur in minutes after preexposure to 10(-6) M nicotine at 37 degrees C. The depression of catecholamine release upon preexposure to nicotine is both dose and temperature dependent and is not seen with potassium-evoked release. Chronic exposure to 10(-7) M nicotine for 3 days led to a depression of the secretory response to approximately 70% of control responses. There was a trend toward recovery of full response by days 5 and 7 of 10(-7) M nicotine preexposure. Nearly complete depression of the nicotine-evoked release occurs within the first day of exposure to 10(-6) M nicotine and persists for at least a week of nicotine exposure at 37 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)
Bullock
A E
AE
Department of Pharmacology and Toxicology, Albany Medical College, New York.
Barke
K E
KE
Schneider
A S
AS
D000109:Acetylcholine / Q000494:pharmacology; D000313:Adrenal Medulla / Q000187:drug effects* / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D004246:Dimethylphenylpiperazinium Iodide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D007700:Kinetics; D009538:Nicotine / Q000633:toxicity*; D009638:Norepinephrine / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology; D012907:Smoking; D013997:Time Factors
D004246:Dimethylphenylpiperazinium Iodide; D009538:Nicotine; D000109:Acetylcholine; D011188:Potassium; D002118:Calcium; D009638:Norepinephrine