Protein interactions and metabolic response to stimulating agents in isolated cerebral tissues: histones as inhibitors

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Abstract
Extracts from cerebral tissues were tested for action on respiration of guinea-pig cerebral cortex incubated in glucose-containing media. An extract made with acid contained non-dialyzable material which inhibited the tissue''s response to applied electrical pulses, though it had little effect on respiration in the absence of pulses. The inhibitory material is probably a histone. Similar material was obtained by NaCl ethanol extraction, and by extraction of nuclear fractions of the tissue. Histone and protamine preparations from other sources were also inhibitory, being active when incorporated in media at about 5[mu][image]. They inhibited the tissue''s glycolytic response to pulses and its glycolytic and respiratory responses to 50 m[image]-K salts. The blood-plasma fraction IV-4 which restored response to cerebral tissues after they had been rendered unresponsive by being kept at 0[degree] restored response also to tissues treated with protamine and histone. Fraction IV-4 formed precipitates with the basic proteins, and with the inhibitory cerebral extracts, but not with a number of non-inhibitory cerebral extracts. Time factors in the action of the protamine and histone preparations were investigated. The tissue''s histone is apparently involved in the loss of excitability which occurs when cerebral tissues are kept in cold media.