ABNORMAL NOREPINEPHRINE METABOLISM IN RAT-BRAIN SYNAPTOSOMES IN PHOSPHATE-DEPLETION

Abnormalities in the function of the central nervous system exist in p hosphate depletion (PD). It is possible that this is due to an adverse effect of PD on the metabolism of neurotransmitters, such as norepine phrine (NE), in brain synaptosomes. We examined the effects of PD, pro duced by restriction of dietary phosphate intake on NE metabolism of b rain synaptosomes. Synaptosomes from PD rats had significantly reduced NE content, uptake and release, elevated K(m), but normal V(max) of t yrosine hydroxylase, normal K(m) and V(max) of monoamine oxidase, elev ated resting levels of cytosolic calcium ([Ca2+]i), higher DELTA[Ca2+] i in response to KCl, higher DELTA[Ca2+]i/basal [Ca2+]i ratio, lower A TP content and reduced activity of Na+-K+-ATPase as compared to synapt osomes from pair-weighed rats. Treatment of PD rats with verapamil cor rected all the synaptosomal derangements except for the elevated K(m) of tyrosine hydroxylase and NE content. Verapamil did not affect the m etabolism of PW rats. The data demonstrate that PD causes significant derangements in NE metabolism of brain synaptosomes. Observations in t he present study and in others indicate that these derangements in NE metabolism are due to the PD-induced abnormalities in the homeostasis of synaptosomal [Ca2+]i, ATP and phospholipids and in the activities o f Na+-K+-ATPase and Ca2+-ATPase.