We recently identified two cDNA-encoded paralogous small secretory proteins: neurosecretory protein GL (NPGL) and neurosecretory protein GM (NPGM) in the chick hypothalamic infundibulum.¹ We also detected homologous genes in the vertebrate genome. In a preliminary study, we found that NPGM-producing cells were present among the histaminergic neurons in the rat brain. Although it has been established that histamine is synthesized by the enzyme histidine decarboxylase (HDC) in mammals, the function of HDC and histaminergic neurons in the avian brain have not yet been characterized. To study this aspect, we first cloned the HDC cDNA from the hypothalamus of a chicken. We found that the expressed protein possessed a high level of enzymatic activity. Quantitative RT-PCR analysis showed that the HDC mRNA was highly expressed in the hypothalamic infundibulum. In situ hybridization analysis revealed that the cells containing HDC mRNA were localized to the medial mammillary nucleus (MM) of the hypothalamic infundibulum.

We subsequently raised a specific antibody against chick NPGM and examined the localization of NPGM-producing cells by immunohistochemical analysis. NPGM-like immunoreactive cells were distributed across the MM and the infundibular nucleus of the hypothalamus. In order to clarify the relationship between histamine and NPGM, we compared the localization of histaminergic neurons and NPGM-producing cells. We observed that histamine and NPGM were produced in the same neurons located in the MM. A quantitative PCR analysis showed that mRNA levels of HDC and NPGM in the hypothalamic infundibulum increased during fasting and decreased during post-hatching development. An intracerebroventricular injection of histamine or NPGM in chicks inhibited feeding behavior. These results suggest that histamine and NPGM, which are produced by the same neurons in the chicken brain, exhibit functional complementarity.