CELLULAR-DISTRIBUTION OF NEUROTENSIN RECEPTORS IN RAT-BRAIN - IMMUNOHISTOCHEMICAL STUDY USING AN ANTIPEPTIDE ANTIBODY AGAINST THE CLONED HIGH-AFFINITY RECEPTOR

Receptors for the neuropeptide, neurotensin, were localized by immunoh istochemistry in the rat brain by using an antibody raised against a s equence of the third intracellular loop of the cloned high affinity re ceptor. Selective receptor immunostaining was observed throughout the brain and brainstem. This immunostaining was totally prevented by prea dsorbing the antibody with the immunogenic peptide. The regional distr ibution of the immunoreactivity conformed for the most part to that of [H-3]- or [I-125]-neurotensin binding sites previously identified by autoradiography. Thus, the highest levels of immunostaining were obser ved in the islands of Calleja, diagonal band of Broca, magnocellular p reoptic nucleus, pre- and parasubiculum, suprachiasmatic nucleus, ante rodorsal nucleus of the thalamus, substantia nigra, ventral tegmental area, pontine nuclei and dorsal motor nucleus of the vagus, all of whi ch had previously been documented to contain high densities of neurote nsin binding sites. There were, however, a number of regions reportedl y endowed with neurotensin binding sites, including the central amygda loid nucleus, periaqueductal gray, outer layer of the superior collicu lus and dorsal tegmental nucleus, which showed no or divergent pattern s of immunostaining, suggesting that they might be expressing a molecu larly distinct form of the receptor. At the cellular level, neurotensi n receptor immunoreactivity was predominantly associated with perikary a and dendrites in some regions (e.g., in the basal forebrain, ventral midbrain, pens and rostral medulla) and with axons and axon terminals in others (e.g., in the lateral septum, bed nucleus of the stria term inalis, neostriatum, paraventricular nucleus of the thalamus and nucle us of the solitary tract). These data indicate that neurotensin may ac t both post- and presynaptically in the central nervous system and con firm that some of its effects are exerted on projection neurons. There were also areas, such as the cerebral cortex, nucleus accumbens and p ara- and periventricular nucleus of the hypothalamus, which contained both immunoreactive perikary/dendrites and axon terminals, consistent with either a joint association of the receptor with afferent and effe rent elements or its presence on interneurons. Taken together, these r esults also suggest that the neurotensin high affinity receptor protei n is associated with a neuronal population that is more extensive than originally surmised from in situ hybridization studies. (C) 1996 Wile y-Liss, Inc.