Effect of Bay K 8644, calcimycin and phorbol ester on radiation-induced decreases in the release of norepinephrine in the hippocampus in rats.
Gamma radiation (10 Gy at 10 Gy/min from a 60Co source) induces a decrease in the release of norepinephrine in the hippocampus 48 h after exposure. The purpose of this study was to determine the effect of Bay K 8644 [methyl-1,4-dihydro-2,6-dimethyl-3-nitro-4-2(trifluoromethylphenyl)py rid ine-5-carboxylate], an agonist for L- and N-type calcium channel subtypes; calcimycin [6S-[6alpha(2S*,3S*),8beta(R*),9beta,11alpha]-5( methylamino)-2-[[3,9,11-trimethyl-8-[1-methyl-2-oxo-2(1H-pyrrol-2-yl)eth yl]-1,7-dioxaspiro[5,5]undec-2-yl]methyl]-4-benzoxazoleca rboxylic acid], a calcium ionophore which increases intracellular Ca2+; and phorbol 12-O-tetradecanoate 13-acetate (TPA), which stimulates protein kinase C (PKC) alone or in combination with decreases in the release of norepinephrine in the hippocampus 48 h after irradiation. Neither Bay K 8644 (1-100 nM), calcimycin nor TPA prevented the radiation-induced decreases in the release of norepinephrine in the hippocampus. However, 10 nM of Bay K 8644 or calcimycin in combination with 1-100 nM of TPA or 10 nM of TPA in combination with 1-100 nM of Bay K 8644 or calcimycin did prevent the radiation-induced decreases in the release of norepinephrine. These results suggest that stimulation of PKC by TPA and mobilization of calcium by Bay K 8644 or calcimycin are necessary to prevent the radiation-induced decreases in the release of norepinephrine in the hippocampus.
Kandasamy
S B
SB
Radiation Pathophysiology and Toxicology Department, Armed Forces Radiobiology Research Institute, Bethesda, Maryland 20889-5145, USA.
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology*; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology*; D002118:Calcium / Q000502:physiology*; D002120:Calcium Channel Agonists / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005720:Gamma Rays; D006624:Hippocampus / Q000378:metabolism / Q000528:radiation effects*; D007476:Ionophores / Q000494:pharmacology*; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D010703:Phorbol Esters / Q000494:pharmacology*; D011493:Protein Kinase C / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley
D002120:Calcium Channel Agonists; D007476:Ionophores; D010703:Phorbol Esters; D000001:Calcimycin; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D011493:Protein Kinase C; D002118:Calcium; D009638:Norepinephrine