Studies of mechanisms of chemical radiation protection in vivo. I. 5-Hydroxytryptamine in relation to effect of antimetabolites, antagonists and releasing agents.

Abstract

The radioprotective action of 5-hydroxytryptamine (5HT) in rats is specifically reversed by 5HT antimetabolites and antagonists of the b- haloalkylamine group, which block D receptors on smooth muscle cells. This reversal is not obtained with those antihistamines that have a very weak antiserotonin activity, despite their reversal of histamine protection. There is no correlation between the extractable 5HT in rat tissues, using bioassay techniques, and the radioprotection induced by exogenous administration of 5HT, by the anti-5HT-brominated lysergic acid (BOL), or by reserpine, singly or in combination. The sudden endogenous release of tissue 5HT gives radio-protection, but depletion of such endogenous 5HT by reserpine fails to alter radiosensitivity in vivo. There is no correlation between hypothermia and radiosensitivity of rats in respect to 5HT and reserpine. The precursor of 5HT in metabolism, 5hydroxytryptophan as the L antipode, fails to afford protection against ionizing radiations quantitatively similar to 5HT: the slight protection which results is probably due to the formation of the amine in vivo following decarboxylation. The results fail to support the protective action of 5HT in terms of either radical capture or the formation of radio-resistant amine-macromolecule complexes. The results favor a simple exposition of 5-hydroxytryptamine protection in terms ofmore » pharmacologically induced tissue anoxia and a reduction in the oxygen effect. (auth)« less