Histamine synthesis in the developing rat brain: evidence for a multiple compartmentation.

Subcellular fractionation techniques, radio-labeling by the 3H-precursor and pharmacological approach applied to the developing rat indicate the presence of at least two types of histamine-containing cells in brain. The presence of the histamine synthesizing enzyme in neurons is suggested by its developmental pattern: there is a 4- to 5-fold increase in enzyme activity from birth to adulthood, with a time-course paralleling the synaptogenesis in whole brain as well as in the 4 regions studied (medulla-pons, midbrain, hypothalamus and forebrain). As is the case for different transmitter synthesizing enzymes such as tyrosine hydroxylase, there is a shift in the subcellular distribution of histidine decarboxylase (H.D.) activity from the soluble fraction at birth to the synaptosomal fraction in the adult brain. On the other hand, several lines of evidence indicates that a portion of histamine is localized, at least in the noenatal rat brain, in mast cells: (a) the high level of histamine in the neonatal rat brain is, like in peripheral mast-cells, associated with a low enzyme activity; (b) the half-life of [3H]histidine injected s.c. at birth was about 4 days, a value close to that found in skin (a tissue rich in mast cells), but contrasting with that in adult brain (less than 1 h); (c) after subcellular fractionation, the endogenously formed [3H]histamine was recovered in the crude nuclear fraction as was the amine from peritoneal mast cells added to the brain homogenate; (d) the mast cell degranulators, compound 48/80 and polymyxin B, induce a small but significant release of the amine from incubated neonatal brain slices. Thus it appears that cerebral histamine is localized in at least two cell types. Its presence in neurons is compatible with a neurotransmitter function and its release from mast cells might represent some primitive form of cell-to-cell communication.