Specific binding and internalization of blood-borne [125I]-iodoinsulin by neurons of the rat area postrema.

Abstract

The specificity and cellular location of binding sites for blood-borne [125I]iodoinsulin in the area postrema and adjacent paravagal region of the rat brain was determined by means of quantitative light and electron microscope radioautography. In both regions coinjected unlabeled insulin inhibited the binding of [125I]iodoinsulin in a dose-dependent manner, and insulin analogs blocked [125I]iodoinsulin binding in rank order of their known in vitro bioactivity. Electron microscope radioautography of this region showed that insulin specifically bound to neuronal dendrites and cell bodies and that some of the specifically bound radioactivity was internalized and concentrated in a variety of subcellular vacuoles. These observations demonstrate that certain neurons of the area postrema are endowed with the receptive capacity common to all known insulin-sensitive cells. Anatomic considerations suggest that insulin target neurons in the area postrema could mediate insulin feedback on parasympathetic function by relaying information regarding circulating insulin status to central autonomic circuits governing vagal activity. This study represents the first demonstration of a receptor-mediated uptake and concentration of a blood-borne polypeptide hormone by central neurons.