Influence of naloxone on catecholamine release evoked by nicotinic receptor stimulation in the isolated rat adrenal gland.
The present study was designed to investigate the effect of naloxone, a well known opioid antagonist, on the secretion of catecholamines (CA) evoked by cholinergic stimulation and membrane-depolarization in the isolated perfused rat adrenal glands, and to establish its mechanism of action. Naloxone (10(-6) approximately 10(-5) M), perfused into an adrenal vein for 60 min, produced dose- and time-dependent inhibition of CA secretory responses evoked by ACh (5.32 x 10(-3) M), high K+ (5.6 x 10(-2) M), DMPP (10(-4) M) and McN-A-343 (10(-4) M). Naloxone itself also failed to affect the basal CA output. In adrenal glands loaded with naloxone (3 x 10(-6) M), the CA secretory responses evoked by Bay-K-8644, an activator of L-type Ca2+ channels, and cyclopiazonic acid, an inhibitor of cytoplasmic Ca(2+)-ATPase, were also inhibited. In the presence of met-enkephalin (5 x 10(-6) M), a well known opioid agonist, the CA secretory responses evoked by ACh, high K+, DMPP, McN-A-343, Bay-K-8644 and cyclopiazonic acid were also significantly inhibited. Taken together, these results suggest that naloxone greatly inhibits the CA secretion evoked by stimulation of cholinergic (both nicotinic and muscarinic) receptors as well as that by membrane depolarization. It seems that these inhibitory effects of naloxone does not involve opioid receptors, but might be mediated by blocking both the calcium influx into the rat adrenal medullary chromaffin cells and the uptake of Ca2+ into the cytoplasmic calcium store, which are at least partly relevant to the direct interaction with the nicotinic receptor itself.
Kim
Ok-Min
OM
Department of Pharmacology, College of Medicine, Chosun University, Gwangju 501-759, Korea.
Lim
Geon-Han
GH
Lim
Dong-Yoon
DY
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000109:Acetylcholine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000311:Adrenal Glands / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D002395:Catecholamines / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004246:Dimethylphenylpiperazinium Iodide / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004744:Enkephalin, Methionine / Q000008:administration & dosage / Q000494:pharmacology; D007211:Indoles / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008297:Male; D009270:Naloxone / Q000008:administration & dosage / Q000494:pharmacology*; D010477:Perfusion; D011188:Potassium / Q000037:antagonists & inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000187:drug effects* / Q000378:metabolism; D013268:Stimulation, Chemical; D013997:Time Factors
D002395:Catecholamines; D007211:Indoles; D011978:Receptors, Nicotinic; D009270:Naloxone; D004246:Dimethylphenylpiperazinium Iodide; D004744:Enkephalin, Methionine; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D000109:Acetylcholine; D011188:Potassium; C000543:cyclopiazonic acid