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M J Brownstein

Publications and source records attributed to M J Brownstein.

At least 91 records · Page 5Linked to original sources

The distribution of immunoreactive alpha-neo-endorphin in the central nervous system of the rat.

Using a specific radioimmunoassay, we have found that immunoreactive (ir) alpha-neo-endorphin has a widespread and unique distribution in the rat brain and spinal cord. The highest concentration in brain is in the substantia nigra (1692.1 fmol/mg of protein). Very high concentrations of ir-alpha- neo-endorphin (greater than 500 fmol/mg of protein) are also found in the lateral preoptic nucleus, dentate gyrus, parabrachial nuclei, nucleus accumbens, globus pallidus, median eminence, and anterior hypothalamic nucleus. Relatively high concentrations of ir-alpha-neo-endorphin (250 to 500 fmol/mg of protein) are present in the bed nucleus of the stria terminalis, paraventricular nucleus, nucleus of the solitary tract, dorsomedial nucleus, central amygdaloid nucleus, periaqueductal gray matter, suprachiasmatic nucleus, periventricular nucleus, hippocampus, prepositus hypoglossal nucleus, arcuate nucleus, ventromedial nucleus, medial preoptic nucleus, zona incerta, dorsal premamillary nucleus, medial forebrain bundle (hypothalamic and preoptic), nucleus of the diagonal band, locus ceruleus, lateral septal nucleus, and nucleus ambiguus . Moderate levels (100 to 250 fmol/mg of protein) are found in the posterior hypothalamic nucleus, ventral premamillary nucleus, dorsal raphe nucleus, motor hypoglossal nucleus, caudate-putamen, periventricular thalamic nucleus, subcommissural organ, sensory trigeminal nucleus, perifornical nucleus, area postrema, supraoptic nucleus, cuneate nucleus, medial amygdaloid nucleus, and organum vasculosum laminae terminalis. Low concentrations of ir-alpha-neo-endorphin (less than 100 fmol/mg of protein) are found in many cortical structures, claustrum, thalamic nuclei, habenular nuclei, lateral geniculate body, red nucleus, superior and inferior colliculi, paramedian reticular nucleus, pontine nuclei, superior olive, vestibular nuclei, motor facial nucleus, gigantocellular reticular nucleus, and subfornical organ.(ABSTRACT TRUNCATED AT 250 WORDS)

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Distribution of immunoreactive beta-neo-endorphin in discrete areas of the rat brain and pituitary gland: comparison with alpha-neo-endorphin.

The distribution of immunoreactive (ir)-beta-neo-endorphin in 101 microdissected rat brain and spinal cord regions as well as in the neurointermediate lobe of pituitary gland was determined using a highly specific radioimmunoassay. The highest concentration of beta-neo-endorphin in brain was found in the median eminence (341.4 fmol/mg of protein). High concentrations of ir-beta-neo-endorphin (greater than 250 fmol/mg of protein) were found in 11 nuclei, including dorsomedial nucleus, substantia nigra, parabrachial nuclei, periaqueductal gray matter, anterior hypothalamic nucleus, and lateral preoptic areas. Moderate concentrations of the peptide (between 100 and 250 fmol/mg of protein) were found in 66 brain nuclei such as the amygdaloid and septal nuclei, most of the diencephalic structures (not including the hypothalamus), and the majority of the medulla oblongata nuclei and others. Low concentrations of ir-beta-neo-endorphin (less than 100 fmol/mg of protein) were found in 21 nuclei, e.g., cortical structures (frontal., cingulate, piriform, parietal, entorhinal, occipital), olfactory tubercle, and cerebellum (nuclei and cortex). The olfactory bulb has the lowest beta-neo-endorphin concentration (21.3 fmol/mg of protein). Spinal cord segments exhibit low peptide concentrations. The neurointermediate lobe of the pituitary gland is extremely rich in ir-beta-neo-endorphin.

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Onset of neurophysin self-association upon neurophysin/neuropeptide hormone precursor biosynthesis.

The potential of the common biosynthetic precursor of neurophysin and neuropeptide hormones to self-associate has been assessed by quantitative affinity chromatographic analysis. The precursor form, with the hormone sequence in the amino terminal region and assumed able to interact intramolecularly with the hormone binding site of the neurophysin domain of the folded precursor, exhibits an affinity for neurophysin-agarose which is intermediate between those of unliganded neurophysin and non-covalently hormone-liganded neurophysin. The results lead to a prediction that neurophysin self-association is established upon precursor synthesis and prior to limited proteolysis of the precursor to release mature neurophysin and hormone components. Such self-association could play a role in packaging of the precursor into secretory granules and in regulating subsequent precursor processing events within the granules.

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Distribution of immunoreactive dynorphin in the central nervous system of the rat.

A widespread distribution of immunoreactive dynorphin (ir-Dyn) in rat brain and spinal cord was demonstrated by means of a highly specific radioimmunoassay. The highest concentrations of ir-Dyn (greater than 399 pg/mg protein) were found in hypothalamic nuclei, i.e. the premamillary, anterior hypothalamic and dorsomedial nuclei and median eminence. Relatively high concentrations of ir-Dyn (between 320 and 399 pg/mg protein) were found in other hypothalamic nuclei such as the medial and lateral preoptic, perifornical, suprachiasmatic, ventromedial nuclei and in the medulla oblongata in the area postrema and in the nucleus of the solitary tract (commissural part). Moderate levels of ir-Dyn (between 140 and 320 pg/mg protein) were found in most diencephalic areas other than the hypothalamic nuclei and further nuclei in the medulla oblongata, in the mesencephalon, pons and spinal cord. Low to moderate levels of ir-Dyn were found in the telencephalon, with lowest levels (less than 140 pg/mg protein) found in the cerebral cortex, olfactory bulb, dorsal septal nucleus, medial amygdaloid nucleus, caudate-putamen, superior collicle, cerebellum and certain areas of the reticular formation.

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Immunoreactive dynorphin and alpha-neo-endorphin in rat hypothalamo-neurohypophyseal system.

Concentrations of dynorphin and alpha-neo-endorphin were measured in rat supraoptic and paraventricular nuclei, median eminence and posterior pituitary. Paraventricular lesions did not alter the level of either peptide in the median eminence or posterior pituitary. Knife cuts in the lateral retrochiasmatic area that severed the supraoptico-hypophyseal tract reduced dynorphin and alpha-neo-endorphin levels by 64-80% in the posterior pituitary and by somewhat less in the median eminence. Knife cuts in the vicinity of the supraoptic nucleus that did not interrupt the supraoptico-hypophyseal tract did not affect peptide concentrations in the posterior pituitary. Our data suggest that dynorphin and alpha-neo-endorphin in the posterior pituitary are in processes of supraoptic nucleus neurons. These neurons also project to the median eminence which may receive fibers from other dynorphin and alpha-neo-endorphin containing cells too.

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Cholecystokinin peptides in the brain and pituitary of the bullfrog Rana catesbeiana: distribution and characterization.

The distribution of CCK peptides in the bullfrog brain was determined with a CCK radioimmunoassay. Frog brain CCK distribution resembles rat porcine and human brain in that CCK concentration is moderate to high in hypothalamus, diencephalon, and medulla (3 18.4 ng/mg protein) and low in cerebellum (0.6 ng/mg protein). However, unlike all mammalian species examined, the CCK content of frog cerebral cortex, hippocampus and olfactory lobe is quite low (0.03 0.23 ng/mg protein). The elution of CCK-like peptides in frog brain extracts was determined on two HPLC systems. On both systems the bulk of the CCK-like material eluted with CCK 8 sulfate and separated from gastrin and other CCK peptides. These data suggest that though the chemical structure of CCK appears to be the same in the brains of frogs and mammals, the distribution of CCK in the brain appears to have shifted during the course of evolution, becoming a cortical, hippocampal, and olfactory system peptide only in more evolved organisms.

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Direct stimulation of beta 2-adrenergic receptors in rat anterior pituitary induces the release of adrenocorticotropin in vivo.

Previous work in our laboratory has shown that stimulation of beta 2-adrenergic receptors on mouse anterior pituitary tumor cells causes the secretion of immunoreactive adrenocorticotropin (ACTH). The present study was designed to test the hypothesis that catecholamines can cause the release of ACTH in vivo by the direct stimulation of beta 2-adrenergic receptors in the rat anterior pituitary. Systemic administration of a beta-adrenergic receptor agonist (-)-isoproterenol resulted in an increase in plasma ACTH levels in intact animals and in rats with transected pituitary stalks. This effect could be blocked by the beta-adrenergic receptor antagonist, propranolol, but not by the specific beta 1-adrenergic receptor antagonist, practolol. Salmefamol, a beta 2-adrenergic receptor agonist also elevated plasma ACTH levels in stalk-sectioned animals. Dexamethasone, a glucocorticoid that inhibits the synthesis and release of ACTH from the anterior pituitary but not the intermediate lobe, prevented the elevation of ACTH secretion by (-)-isoproterenol in stalk-transected rats. These data indicate that beta 2-adrenergic receptors are present on anterior pituitary cells and suggest that catecholamines can directly stimulate ACTH secretion.

Adrenocorticotropic Hormone↗

Quantitation of changes in the content of neurohypophyseal peptides in hypothalamic nuclei after adrenalectomy.

In adrenal insufficiency there is an increase in the content of vasopressin in the external zone of the median eminence as determined by immunohistology. We studied rats after bilateral adrenalectomy and obtained punched samples of the supraoptic, the paraventricular, and the suprachiasmatic nuclei, and from the median eminence and the posterior pituitary. Vasopressin, neurophysin and oxytocin were all decreased in content in the posterior pituitary but in the suprachiasmatic nucleus and in the median eminence there was a significant increase in the content of vasopressin. The increased levels of vasopressin in the median eminence are interpreted as representative of the content in axons and demonstrate a large increase of transport of vasopressin. In the SON and PVN there was no increase in the content of vasopressin during this state of augmented synthesis and transport, indicating that vasopressin moves rapidly from the site of synthesis into the transport system. The increased content of vasopressin in the suprachiasmatic nucleus shows that vasopressin at this level also varies with changes in adrenal function. Levels of oxytocin throughout the neurohypophysis did not change in parallel with vasopressin demonstrating relatively selective responses of the neurohypophyseal hormones.

Adrenalectomy↗

Corticotropin releasing factor (CRF) immunoreactivity in hypothalamic and extrahypothalamic nuclei of sheep brain.

In sheep, 26 brain areas of 62 investigated contained corticotropin releasing factor (CRF)-like immunoreactivity in concentrations higher than 0.5 ng CRF/mg protein. Most of the CRF in the brain was in the hypothalamus. The highest level of CRF in the sheep brain was in the median eminence, almost two orders of magnitude higher than anywhere else. All of the hypothalamic nuclei had measureable amounts of CRF. A number of extrahypothalamic regions such as amygdala, hippocampus, claustrum, cingulate cortex, habenula and certain lower brainstem nuclei had CRF but generally in very low concentrations.

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Serotonergic innervation of the rat pituitary intermediate lobe: decrease after stalk section.

Serotonin (5-HT)-containing nerve fibers and terminals, but not cell bodies, have been demonstrated by light and electron microscopic immunocytochemistry in the intermediate lobe of the rat pituitary. Seven days after pituitary stalk transection, 5-HT immunoreactive fibers disappeared almost entirely from the intermediate lobe. Intermediate lobe 5-HT and 5-hydroxyindoleacetic acid concentrations, measured by high pressure liquid chromatography coupled to electrochemical detection, fell to 56% and 62% of control, respectively. There were no changes in 5-HT concentrations in anterior or posterior lobes of the pituitary or in the median eminence. These findings, and the failure of sympathectomy to cause a drop in pars intermedia 5-HT, indicate that in the intermediate lobe of the pituitary neuronal 5-HT originates in cells situated in the central nervous system.

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Regional distribution of substance P-like immunoreactivity in the lower brainstem of the rat.

A radioimmunoassay was used to quantify substance P-like immunoreactivity in the lower brainstem of the rat. The peptide was detectable in all brainstem nuclei investigated. A very high concentration was found in the substantia nigra, and high concentrations in the interpeduncular nucleus and central gray matter. Levels in the pons, the parabrachial nuclei; in the medulla, the nucleus tractus spinalis of the Vth nerve and the nucleus of the solitary tract were higher than the brain average.

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