Inhibition by neuroprotective drug NS-7 of nicotine-induced 22Na(+) influx, 45Ca(2+) influx and catecholamine secretion in adrenal chromaffin cells.
In cultured bovine adrenal chromaffin cells, NS-7 [4-(4-fluorophenyl)-2-methyl-6-(5-piperidinopentyloxy) pyrimidine hydrochloride], a newly-synthesized neuroprotective drug, inhibited nicotine-induced 22Na(+) influx via nicotinic receptors (IC(50)=15.5 microM); the suppression by NS-7 was observed in the presence of ouabain, an inhibitor of Na(+),K(+)-ATPase, and was not attenuated upon the washout of NS-7. NS-7 decreased nicotine-induced maximum influx of 22Na(+) without altering the EC(50) value of nicotine. Also, NS-7 diminished nicotine-induced 45Ca(2+) influx via nicotinic receptors and voltage-dependent Ca(2+) channels (IC(50)=14.1 microM) and catecholamine secretion (IC(50)=19.5 microM). These results suggest that NS-7 produces noncompetitive and long-lasting inhibitory effects on neuronal nicotinic receptors in adrenal chromaffin cells, and interferes with the stimulus-secretion coupling.
Department of Pharmacology, Miyazaki Medical College, Japan.
H
H
Yokoo
S
S
Shiraishi
H
H
Kobayashi
T
T
Yanagita
S
S
Minami
R
R
Yamamoto
A
A
Wada
D000311:Adrenal Glands / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002132:Calcium Radioisotopes; D002395:Catecholamines / Q000037:antagonists & inhibitors; D002417:Cattle; D002478:Cells, Cultured; D019439:Chromaffin Cells / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D010042:Ouabain / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology*; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000378:metabolism; D012964:Sodium / Q000037:antagonists & inhibitors*; D012979:Sodium Radioisotopes; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors
C106144:4-(4-fluorophenyl)-2-methyl-6-(5-piperidinopentyloxy)pyrimidine hydrochloride; D002121:Calcium Channel Blockers; D002132:Calcium Radioisotopes; D002395:Catecholamines; D004791:Enzyme Inhibitors; D018696:Neuroprotective Agents; D018722:Nicotinic Agonists; D011743:Pyrimidines; D011978:Receptors, Nicotinic; D012979:Sodium Radioisotopes; D010042:Ouabain; D009538:Nicotine; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D002118:Calcium