Functional aspects of calcium channels of splanchnic neurons and chromaffin cells of the rat adrenal medulla.
Effects of the inorganic calcium channel blockers zinc, manganese, cadmium, and nickel on secretion of catecholamines from the perfused adrenal gland of the rat were investigated. Secretion of catecholamines evoked by splanchnic nerve stimulation (1 and 10 Hz) was not affected by nickel (100 microM), partially blocked (50%) by cadmium (100 microM), and almost completely blocked (90%) by zinc (1 mM) or manganese (2 mM). A combination of nickel and cadmium inhibited nerve stimulation-evoked secretion by 80-90%. Catecholamine secretion evoked by direct stimulation of chromaffin cells by acetylcholine (50 micrograms), nicotine (5 microM), muscarine (50 micrograms), and K+ (17.5 mM) was not blocked by either cadmium, nickel, or their combination. However, zinc and manganese almost abolished nicotine- and K(+)-evoked secretion of catecholamines. None of the above agents had any effect on the secretion evoked by muscarine. Acetylcholine-evoked secretion of catecholamines was only partially reduced (50%) by zinc and manganese. We draw the following conclusions from the above findings: (a) cadmium plus nickel selectively blocks the calcium channels of splanchnic neurons but has no effect on calcium channels of the chromaffin cells; (b) zinc and manganese do not discriminate between calcium channels of neurons and calcium channels of chromaffin cells; (c) partial inhibition of acetylcholine-evoked secretion by inorganic calcium channel blockers is consistent with the idea that activation of nicotinic receptors increases Ca2+ influx, and activation of muscarinic receptors mobilizes intracellularly bound Ca2+, which is not affected by calcium channel blockers.
Shukla
R
R
Department of Pharmacology, Wayne State University, Detroit, Michigan 48201.
Wakade
A R
AR
D000109:Acetylcholine / Q000494:pharmacology; D000313:Adrenal Medulla / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism*; D002395:Catecholamines / Q000378:metabolism; D002838:Chromaffin System / Q000166:cytology / Q000378:metabolism*; D004558:Electric Stimulation; D008297:Male; D009116:Muscarine / Q000494:pharmacology; D009474:Neurons / Q000378:metabolism*; D009538:Nicotine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D013153:Splanchnic Nerves / Q000166:cytology / Q000378:metabolism*
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D002395:Catecholamines; D009538:Nicotine; D009116:Muscarine; D000109:Acetylcholine; D011188:Potassium