Metabolism of carnosine and homocarnosine in subcellular fractions and neuronal and glial cell‐enriched fractions of rabbit brain

THE L-histidine-containing dipeptides carnosine (p-alanylL-histidine) and homocarnosine (y-aminobutyryl-L-histidine) are found in excitable tissue, where their function remains an enigma. In 1900, GULEWITSCH & AMIRADZIBI (1900) discovered carnosine in muscle. Homocarnosine was identified by PISANO et at. (1961) in bovine brain. ABRAHAM et al. (1962) found homocarnosine in pig, dog, cat and man to be present exclusively in the CNS. The same workers also reported the presence of small amounts of carnosine in brain tissue. The synthesis 'in vitro and in uivo of homocarnosine and carnosine were demonstrated in frog brain by YOCKEY & MARSHALL (1969). NG & MARSHALL (1976) showed that homocarnosinecarnosine synthetase [L-histidine: b-alanine ligase (AMP) (EC 6.3.2.1 l)] was present in the brains of mouse, chick, rat and frog. On neural function, it was suggested (MAROOLIS, 1974, 1975; NEIDLE & KANDERA, 1974) that carnosine may serve as a neurotransmitter in the primary olfactory pathway. Recently, NEIDLE & MAROOLIS (1976) reported that the mouse brain had a much faster turnover of carnosine than the muscle; both tissues have comparable concentrations of carnosine. These investigators also suggested that carnosinehomocarnosine dependent neuronal pathways are not restricted to the olfactory system, but might be present in the entire CNS. The neurochemical approach to establish a neurotransmitter is to study its synthesis, release, postsynaptic action and inactivation [APRISON & WERMAN, 1968; JOHNSTON, 1976). Little is known about carnosine and homocarnosine in terms of localization of synthetic or degradative processes. Therefore, a comparison of dipeptide metabolism in subcellular fractions and neuronal and glial cell-enriched fractions may yield information on metabolic compartmentation and function of the dipeptides in the CNS.