Effects of Ca2+ channel antagonists on acetylcholine and catecholamine releases in the in vivo rat adrenal medulla.
To elucidate the types of voltage-dependent Ca(2+) channels controlling ACh and catecholamine releases in the in vivo adrenal medulla, we implanted microdialysis probes in the left adrenal medulla of anesthetized rats and investigated the effects of Ca(2+) channel antagonists on ACh, norepinephrine, and epinephrine releases induced by nerve stimulation. The dialysis probes were perfused with Ringer solution containing a cholinesterase inhibitor, neostigmine. The left splanchnic nerves were electrically stimulated at 2 and 4 Hz before and after intravenous administration of Ca(2+) channel antagonists. omega-Conotoxin GVIA (an N-type Ca(2+) channel antagonist, 10 microg/kg) inhibited ACh release at 2 and 4 Hz by approximately 40%, norepinephrine release at 4 Hz by approximately 50%, and epinephrine release at 2 and 4 Hz by approximately 45%. A fivefold higher dose of omega-conotoxin GVIA (50 microg/kg) did not further inhibit these releases. omega-Conotoxin MVIIC (a P/Q-type Ca(2+) channel antagonist, 50 microg/kg) inhibited ACh and epinephrine releases at 4 Hz by approximately 30%. Combined omega-conotoxin GVIA (50 microg/kg) and MVIIC (250 microg/kg) inhibited ACh release at 2 and 4 Hz by approximately 70% and norepinephrine and epinephrine releases at 2 and 4 Hz by approximately 80%. Nifedipine (an L-type Ca(2+) channel antagonist, 300 and 900 microg/kg) did not change ACh release at 2 and 4 Hz; however, nifedipine (300 microg/kg) inhibited epinephrine release at 4 Hz by 20%, and nifedipine (900 microg/kg) inhibited norepinephrine and epinephrine releases at 4 Hz by 30%. In conclusion, both N- and P/Q-type Ca(2+) channels control ACh release on preganglionic splanchnic nerve endings while L-type Ca(2+) channels do not. L-type Ca(2+) channels are involved in norepinephrine and epinephrine releases on chromaffin cells.
Akiyama
Tsuyoshi
T
Dept. of Cardiac Physiology, National Cardiovascular Center Research Institute, 5-7-1 Fujishiro-dai, Suita, Osaka, 565-8565 Japan. takiyama@ri.ncvc.go.jp
Yamazaki
Toji
T
Mori
Hidezo
H
Sunagawa
Kenji
K
D000109:Acetylcholine / Q000378:metabolism*; D000313:Adrenal Medulla / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002395:Catecholamines / Q000378:metabolism*; D004558:Electric Stimulation; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D017551:Microdialysis; D009411:Nerve Endings / Q000187:drug effects / Q000378:metabolism; D009543:Nifedipine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013153:Splanchnic Nerves / Q000502:physiology; D020866:omega-Conotoxin GVIA / Q000494:pharmacology; D020960:omega-Conotoxins / Q000494:pharmacology
D002121:Calcium Channel Blockers; D002395:Catecholamines; D020960:omega-Conotoxins; C075851:omega-conotoxin-MVIIC; D020866:omega-Conotoxin GVIA; D009543:Nifedipine; D000109:Acetylcholine