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.