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)
Department of Pharmacology, College of Medicine, Hallym University, Chunchon, South Korea.
H W
HW
Suh
P M
PM
Hudson
M K
MK
McMillian
K P
KP
Das
B C
BC
Wilson
G C
GC
Wu
J S
JS
Hong
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives*; D000313:Adrenal Medulla / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D002417:Cattle; D018680:Cholinergic Antagonists / Q000494:pharmacology; D015342:DNA Probes; D004744:Enkephalin, Methionine / Q000378:metabolism*; D004745:Enkephalins / Q000235:genetics*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D008969:Molecular Sequence Data; D009538:Nicotine / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology*; D009553:Nimodipine / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011498:Protein Precursors / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects
D018680:Cholinergic Antagonists; D015342:DNA Probes; D004745:Enkephalins; D004791:Enzyme Inhibitors; D007093:Imidazoles; D007546:Isoquinolines; D018722:Nicotinic Agonists; D010879:Piperazines; D011498:Protein Precursors; D012333:RNA, Messenger; C029992:proenkephalin; C031938:calmidazolium; D009553:Nimodipine; D004744:Enkephalin, Methionine; C063302:KN 62; D009538:Nicotine; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D017871:Calcium-Calmodulin-Dependent Protein Kinases