Histochemical studies on endothelin and the endothelin-A receptor in the hypothalamus

By use of a rabbit polyclonal antibody specific to the endothelin-A (ETA) receptor, we analyzed the distribution of neurons containing ETA receptors in rat brain. Almost all A1-A7 noradrenergic neurons, A8-A16 and retinal amacrine (A17) dopaminergic neurons (except the A15 group), and C3 adrenergic neurons contained ETA receptors. In addition, hypothalamic magnocellular (noncatecholaminergic) neurons also showed immunoreactivity to ETA receptors, whereas the staining intensity was low. These observations were confirmed by analyzing the expression of c-fos in the hypothalamus after central injection of ET isopeptides. We also examined immunohistochemically the distribution of big ETs and mature ETs in the hypothalamus. The paraventricular and supraoptic magnocellular neurons in the hypothalamus were immunopositive for big ET-1 and mature ET-1. However, their nerve fibers were immunostained only with antibody to big ET-1. The observations on big ET-1 were altered by colchicine treatment. Considering all the evidence, mature ET-1 may regulate neurotransmission in the hypothalamic region, whereas big ET-1 is secreted from nerve terminals into the vessels as a neurohormone. It is also concluded that ET, one of the "brain-vascular peptides," has a close relationship with the catecholamine neuron system in the brain.