Long-term stimulation of nicotinic receptors is required to increase proenkephalin A mRNA levels and the delayed secretion of [Met5]-enkephalin in bovine adrenal medullary chromaffin cells.

The effects of nicotine on the transcriptional activity of the proENK gene, proenkephalin A (proENK) mRNA levels, and the secretion of [Met5]-enkephalin (ME) were studied in bovine adrenal medullary chromaffin (BAMC) cells. Nicotine (10 microM) caused an immediate secretion (within 1 hr) of ME followed by a delayed secretion (12-24 hr after treatment) into the medium. Posttreatment with the cholinergic antagonists, hexamethonium (1 mM) and atropine (1 microM), up to 6 hr after the nicotine treatment significantly inhibited the delayed secretion of ME induced by nicotine. However, nicotine-induced long-term secretion of ME was not affected when cholinergic antagonists were added 9 or 12 hr after the nicotine treatment. Long-term (24 hr) stimulation of BAMC cells with nicotine also increased proENK mRNA level. This nicotine-induced response was inhibited by posttreatment with cholinergic antagonists 0.5, 1, 3 and 6 hr after the nicotine treatment. As with the secretion experiments, these cholinergic antagonists did not affect the nicotine-induced responses when they were added at 9 and 12 hr. Posttreatment with nimodipine (1 microM), calmidazolium (1 microM) or KN-62 (5 microM) up to 6 hr after the nicotine treatment significantly inhibited the increases of the long-term secretion of ME and proENK mRNA level induced by nicotine. However, these agents were ineffective in blocking the long-term secretion of ME and proENK mRNA level induced by nicotine when BAMC cells were posttreated after 9 and 12 hr.(ABSTRACT TRUNCATED AT 250 WORDS)