EXPRESSION OF HISTIDINE-DECARBOXYLASE AND CELLULAR HISTAMINE-LIKE IMMUNOREACTIVITY IN RAT EMBRYOGENESIS

In this study we investigated the developmental expression of histidin e decarboxylase (HDC) mRNA and the distribution of histamine-immunorea ctive (histamine-ir) cells in the rat embryonic tissues. We applied No rthern blot analysis, in situ hybridization with synthetic oligonucleo tide probes complementary to the rat HDC cDNA, and indirect histamine immunocytochemistry. Northern blot analysis revealed the appearance of a major (2.6 KB) HDC mRNA species in liver on embryonic Day 14. Its h ybridization level peaked on Day E18, when two minor (1.6 and 3.5 KB) mRNA species were also present. During the periparturition period, a r apid decrease in HDC RNA was apparent, as the 2.6 KB mRNA species was expressed at a low level on postnatal Day P1. The embryonic liver expr essed HDC on days E14-E20. On days E18 and E20, the periosteum and the epiphyseal growth plates of the endochondrally ossificating bones, an d some striated muscle cells, showed hybridization signal for HDC. His tamine immunoreactivity was detected in many epithelial and neuronal c ell types during embryogenesis. An intense histamine immunoreaction ap peared first in essentially all cells of the liver parenchyma on day E 12, This parenchymal histamine immunoreactivity disappeared by birth, after which this immunofluorescence in liver was restricted to a few s cattered mast cells until adulthood. Some neurons in the peripheral se nsory, sympathetic and cranial nerve ganglia were histamine-immunoreac tive from day E16 to birth. In addition, many immunoreactive nerve fib ers were detected in the gastrointestinal muscularis externa, mesenter y, salivary glands, kidney, lung, and muscle tissue. We conclude that during rat embryogenesis histamine is produced and stored transiently by cells in liver, developing bone, and a few striated muscle cells, i n addition to previously reported neurons in rat brain. Many periphera l neurons; epithelial cells, and mast ails display histamine immunorea ctivity during rat embryogenesis but are devoid of detectable HDC mRNA with the current method. It remains possible that histamine is formed by another enzyme or is taken up from the extracellular space. The re sults support the concept that a significant proportion of histamine i s formed and stored by embryonic cells other than mast cells.