Role of potassium channels in catecholamine secretion in the rat adrenal gland.
We elucidated the functional contribution of K(+) channels to cholinergic control of catecholamine secretion in the perfused rat adrenal gland. The small-conductance Ca(2+)-activated K(+) (SK(Ca))-channel blocker apamin (10-100 nM) enhanced the transmural electrical stimulation (ES; 1-10 Hz)- and 1, 1-dimethyl-4-phenyl-piperazinium (DMPP; 5-40 microM)-induced increases in norepinephrine (NE) output, whereas it did not affect the epinephrine (Epi) responses. Apamin enhanced the catecholamine responses induced by acetylcholine (6-200 microM) and methacholine (10-300 microM). The putative large-conductance Ca(2+)-activated K(+) channel blocker charybdotoxin (10-100 nM) enhanced the catecholamine responses induced by ES, but not the responses induced by cholinergic agonists. Neither the K(A) channel blocker mast cell degranulating peptide (100-1000 nM) nor the K(V) channel blocker margatoxin (10-100 nM) affected the catecholamine responses. These results suggest that SK(Ca) channels play an inhibitory role in adrenal catecholamine secretion mediated by muscarinic receptors and also in the nicotinic receptor-mediated secretion of NE, but not of Epi. Charybdotoxin-sensitive Ca(2+)-activated K(+) channels may control the secretion at the presynaptic site.
Laboratory of Pharmacology, Graduate School of Pharmaceutical Sciences, Tohoku University, Aobayama, Sendai, Japan.
T
T
Nagayama
Y
Y
Fukushima
M
M
Yoshida
M
M
Suzuki-Kusaba
H
H
Hisa
T
T
Kimura
S
S
Satoh
D000109:Acetylcholine / Q000494:pharmacology; D000311:Adrenal Glands / Q000378:metabolism*; D000818:Animals; D018999:Charybdotoxin / Q000494:pharmacology; D004246:Dimethylphenylpiperazinium Iodide / Q000494:pharmacology; D004558:Electric Stimulation; D004837:Epinephrine / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology; D018721:Muscarinic Agonists / Q000494:pharmacology; D009498:Neurotoxins / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism*; D010455:Peptides / Q000494:pharmacology; D015221:Potassium Channels / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012604:Scorpion Venoms
D018721:Muscarinic Agonists; D009498:Neurotoxins; D018722:Nicotinic Agonists; D010455:Peptides; D015221:Potassium Channels; D012604:Scorpion Venoms; D016210:Methacholine Chloride; D018999:Charybdotoxin; C008331:mast cell degranulating peptide; D004246:Dimethylphenylpiperazinium Iodide; C077910:margatoxin; D000109:Acetylcholine; D009638:Norepinephrine; D004837:Epinephrine