Vanderhaeghen et al. reported the occurrence of gastrin-like immunoreactivity in the mammalian brain. Subsequent studies have revealed that this immunoreactivity corresponded mainly to the COOH-terminal octapeptide of cholecystokinin (CCK-8), which has a COOH-terminal pentapeptide identical to gastrin. Also, two peptides resembling the NH- and the COOH-terminal tetrapeptide fragments of CCK-8 are present in the central nervous system (CNS). Using COOH-terminal-specific antisera raised to gastrin and/or CCK, the distribution of CCK neurones has been described with immunohistochemical techniques. Although high numbers of cells and nerve terminals are found in cortical areas, the CCK systems are also present in most other parts of the brain and spinal cord. In the CNS, true gastrin molecules, gastrin-17 and gastrin-34 have been located only in the neurohypophysis, hypothalamus and occasionally in the medulla oblongata (unpublished results). We describe here the occurrence of peptides in meso-limbic dopamine neurones in the rat brain. Evidence has also been obtained that mesencephalic dopamine neurones in the human brain contain similar peptides.

The responses of dopamine cells in the substantia nigra to iontophoretically administered dopamine and intravenous apomorphine were compared to the responses of spontaneously active neurons in the caudate nucleus. Dopaminergic cells were six to ten times more sensitive to dopamine and intravenous apomorphine than 86 percent of the caudate cells tested. This differential sensitivity of dopamine auto- and postsynaptic receptors may explain the apparently paradoxical behavioral effects induced by small compared to large doses of some dopamine agonists and may provide a means of developing new types of drugs to antagonize dopaminergic influence in the central nervous system.

The immunoperoxidase technique was used to study the effect of adrenalectomy on vasopressin (VP) immunoreactivity in the hypothalamic paraventricular nucleus of rat. In control animals, relatively few VP-immunostained parvocellular neurons were found in addition to a large population of magnocellular VP neurons. Seven to 14 days after bilateral adrenalectomy, VP immunostaining increased markedly in specific subdivisions of the paraventricular nucleus. In contrast to normal animals, VP immunoreactivity was localized in a large number of parvocellular neurons. Colchicine treatment, on the other hand, did not significantly increase the number of VP-immunostained parvocellular neurons found in control rats. These observations suggest that adrenalectomy increases the number of VP-positive neurons and appears to increase the intensity of VP immunoreactivity specifically in parvocellular neurons. VP parvocellular neurons are confined to those paraventricular nucleus subdivisions that are known to project to the external zone of the median eminence. Moreover, their distribution pattern is very similar, if not identical, to that of the corticotropin-releasing factor (CRF) immunoreactive cells. Parvocellular neurons on adjacent thin sections could be stained for both CRF and VP. Thus, adrenalectomy seems to increase VP staining in CRF immunoreactive parvocellular neurons, which innervate the external zone of the median eminence.Vasopressin (VP) participates in the regulation of corticotropin secretion, potentiating the action of corticotropin-releasing factor (CRF) on the pituitary (1-6). In support of this concept, anatomical studies have shown the presence of a VP fiber system capable of delivering a considerable amount of this peptide to the adenohypophysis (7-10). Neurophysincontaining fibers and varicosities have been described in the vicinity of the portal capillary plexus of the external zone of the median eminence (ME) (5, 10, 11). It is clear now that the majority of these neurophysin-positive axons are vasopressinergic (12,13). Lesion studies indicated that the source of VP to the external zone is the hypothalamic paraventricular nucleus (14,15), although the exact cellular origin of these fibers was unclear.A particularly interesting feature of this system is that adrenalectomy substantially increased VP immunoreactivity in the external zone (13,15,16). This increase could be blocked by glucocorticoid but not by mineralocorticoid treatment (13,17,18). Furthermore, 5 days of dehydration did not affect VP immunostaining in the external zone (13,19). Thus, the increase of VP immunoreactivity after adrenalectomy seems to be due to the lack of glucocorticoid feedback rather than a disturbance in fluid homeostasis. These observations support the hypothesis that VP is involved in the regulation of the pituitary-adrenal axis.In the present study, we sought to determine whether the increased VP immunoreactivity in the external zone after adrenalectomy is accompanied by changes in VP immunostaining in certain su...

Certain neurons in the brain are specifically and intensely stained by a histochemical method which demonstrates nicotinamide adenine dinucleotide phosphate NADPH-diaphorase activity. The cell types containing this enzyme in certain areas of the rat forebrain were examined by combining NADPH-diaphorase histochemistry with the indirect immunofluorescence technique. Neurons containing somatostatin- or avian pancreatic polypeptide (APP)-like immunoreactivities were found throughout the forebrain including the striatum and neocortex. These two neuropeptides were also found to coexist in many telencephalic neurons. After photography, the sections processed for immunohistochemistry were stained for NADPH-diaphorase activity by a histochemical method. It was found that within the striatum all of the neurons that were selectively stained by this technique also contained both somatostatin- and APP-like immunoreactivities. Also in the neocortex NADPH-diaphorase was found only in those neurons displaying somatostatin- or APP-like immunoreactivity. In other brain regions such as the nucleus laterodorsalis tegmenti, NADPH-diaphorase-containing cells did not contain these neuropeptides. The results indicate that NADPH-diaphorase histochemistry provides a simple, reliable, histochemical method to demonstrate those striatal neurons in which somatostatin- and APP-like immunoreactivities coexist. The selective occurrence of this enzyme within these neurons may provide a useful target for pharmacological studies of these neuropeptide-containing cells.

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