Regulation of sympathetic and parasympathetic nerve activities by BIT/SHPS-1.

The hypothalamus plays a central role in the homeostatic regulation of internal physiological conditions such as body temperature and energy balance. We have previously shown that cold exposure enhances tyrosine phosphorylation of BIT/SHPS-1 (brain immunoglobulin-like molecule with tyrosine-based activation motifs/SHP substrate-1) in hypothalamic nuclei including the suprachiasmatic nucleus. In order to elucidate the function of BIT/SHPS-1 in the hypothalamus, we stimulated BIT/SHPS-1 in vivo by using the anti-BIT monoclonal antibody (mAb) 1D4, which reacts with the extracellular domain of BIT/SHPS-1 and induces its tyrosine phosphorylation. Administration of mAb 1D4 into the third cerebral ventricle enhanced the electrical activity of the renal sympathetic nerves, while it suppressed that of the gastric parasympathetic nerves. Similarly, blood pressure increased in response to the mAb 1D4 injection, and additionally, temperatures of the abdomen and brown adipose tissue increased. These results indicate that BIT/SHPS-1 is involved in the hypothalamic regulation of thermogenesis via the autonomic nervous system.