Neurokinin-3 receptor distribution in rat and human brain: An immunohistochemical study

Autoradiographic and immunohistochemical studies have shown that the neurok inin-3 receptor is widely distributed in the rodent CNS. Expression of the neurokinin-3 receptor in human brain, however, has been debated. These conf licting findings, as well as the poor resolution of autoradiographic images , prompted us to develop a polyclonal antibody against an oligopeptide deri ved from the carboxy-terminus consensus sequence of both the rat and human neurokinin-3 receptor ([C]ASTTSS-FISSPYTSVDEYS, amino acids 434-452 of the rat neurokinin-3 receptor). Western blot analysis of both human and rat bra in tissue revealed a major band in the molecular weight range 65,000-67,000 , the proposed molecular weight of the neurokinin-3 receptor based on its a mino acid sequence and presumed glycosylation state. The distribution of se lective high affinity neurokinin-3 receptor agonist [H-3]senktide binding a nd neurokinin-3 receptor immunoreactivity were virtually identical in the b rains of male Fischer 344 rats. The highest concentrations of neurokinin-3 receptors were observed in cortical layers IV-V; the basolateral amygdaloid nucleus; the hypothalamic paraventricular, perifornical and supraoptic nuc lei; the zona incerta; and the entopeduncular and interpeduncular nuclei. [ H-3]senktide binding and neurokinin-3 receptor immunoreactivity were compar ed in homologous cortical areas of the human and rat brain. In contrast to the rat, autoradiographic analysis of normal control human brains (35-75 ye ars) revealed a distinct and predominant superficial cortical labeling in t he glia limitans and the cortical layer I. However, neurokinin-3 receptor i mmunoreactivity could be found not only in the superficial cortical layers, but also on pyramidal neurons and astrocytes in the neuropil and white mat ter. These findings suggest species differences in both the cellular and anatomi cal distribution of the neurokinin-3 receptor. (C) 1999 IBRO. Published by Elsevier Science Ltd.