Apamin-sensitive SK(Ca) channels modulate adrenal catecholamine release in anesthetized dogs.
We investigated the role of high conductance (BK(Ca)) and small conductance Ca2(+)-activated K+ (SK(Ca)) channels in adrenal catecholamine release in response to splanchnic nerve stimulation, acetylcholine, the nicotinic receptor stimulant 1,1-dimethyl-4-phenyl-piperazinium (DMPP), and muscarine in anesthetized dogs. The selective SK(Ca) channel blocker apamin and the selective BK(Ca) channel blocker charybdotoxin were infused into the adrenal gland through the phrenicoabdominal artery, and the cholinergic agonists were injected into the same artery. Splanchnic nerve stimulation (1, 2, 3 and 10 Hz), acetylcholine (0.75, 1.5 and 3 microg), DMPP (0.1, 0.2 and 0.4 microg) and muscarine (0.5, 1 and 2 microg) produced frequency- or dose-dependent increases in catecholamine output as measured in adrenal venous blood. Apamin infusion (1, 3 and 10 ng/min) enhanced the acetylcholine-, DMPP- and muscarine-induced increases in catecholamine output in a dose-dependent manner, but it did not affect the splanchnic nerve stimulation-induced catecholamine response. Charybdotoxin infusion (10, 30 and 100 ng/min) did not affect the increases in catecholamine output induced by the agonists and splanchnic nerve stimulation. Neither apamin nor charybdotoxin affected basal catecholamine output. These results suggest that apamin-sensitive SK(Ca) channels located in adrenal medullary cells may play an inhibitory role in the regulation of adrenal catecholamine release mediated by extrasynaptic nicotinic and muscarinic receptors.
Nagayama
T
T
Department of Pharmacology, Pharmaceutical Institute, Tohoku University, Aobayama, Sendai, Japan.
Koshika
T
T
Hisa
H
H
Kimura
T
T
Satoh
S
S
D000109:Acetylcholine / Q000494:pharmacology; D000311:Adrenal Glands / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D001030:Apamin / Q000494:pharmacology*; D002395:Catecholamines / Q000378:metabolism*; D018999:Charybdotoxin / Q000494:pharmacology*; D004246:Dimethylphenylpiperazinium Iodide / Q000494:pharmacology; D004285:Dogs; D005260:Female; D051036:Large-Conductance Calcium-Activated Potassium Channels; D008297:Male; D009116:Muscarine / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects* / Q000378:metabolism; D024681:Potassium Channels, Calcium-Activated; D013153:Splanchnic Nerves / Q000502:physiology
D002395:Catecholamines; D051036:Large-Conductance Calcium-Activated Potassium Channels; D015221:Potassium Channels; D024681:Potassium Channels, Calcium-Activated; D018999:Charybdotoxin; D001030:Apamin; D004246:Dimethylphenylpiperazinium Iodide; D009116:Muscarine; D000109:Acetylcholine