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Biomedical subjects

S J Watson

Publications and source records attributed to S J Watson.

At least 271 records · Page 15Linked to original sources
PubMed1983

Comparative distribution of opiate receptors and three opioid peptide neuronal systems in rhesus monkey central nervous system.

Using combined autoradiography-immunocytochemistry, the anatomical distribution of [3H]naloxone-labelled opiate receptors was compared to the loci of neuronal systems immunoreactive for beta-endorphin, [Leu]enkephalin and dynorphin A in rhesus monkey brain. High densities of binding were observed in relation to each of the systems, consistent with findings that each opioid precursor can synthesize one or more peptides with substantial (though not selective) activity at mu receptors.

Animals↗
PubMed1983

Immunocytochemistry of the C-terminal peptide of propressophysin (CPP): relationship to vasopressin, oxytocin and neurophysin.

Arginine-vasopressin (AVP) and its associated neurophysin (AVP-NP) are synthesized via a precursor, propressophysin, which also contains a 39 amino acid glycopeptide at its C-terminus (C-terminus of propressophysin, or CPP). In the present study, immunocytochemical techniques were used to determine the cellular co-localization of CPP with AVP, oxytocin (OXY), AVP-NP and OXY-NP in the rat hypothalamus using colchicine pre-treatment and serial 5 micron section analysis. Extensive cross-competition studies of antisera raised against each peptide with the various antigens yielded no significant crossreactivity of the CPP, AVP, OXY and NP antisera. The NP antiserum, although directed against both AVP-NP and OXY-NP, demonstrated a preference for OXY-NP at a dilution of 1:20,000. CPP and AVP were always co-localized within the same magnocellular neurons of the supraoptic, paraventricular and circularis nuclei, and further showed very similar patterning in the suprachiasmatic nucleus as well. In contrast, no cellular overlap could be detected between CPP and OXY, in any of the above nuclei (the suprachiasmatic nucleus is devoid of OXY). Likewise, no examples of co-localization of CPP and OXY-NP were found in the magnocellular nuclei. These results are in strong agreement with a biosynthetic relationship between CPP, AVP and AVP-NP, and their separateness from the OXY and OXY-NP precursor.

Animals↗
PubMed1983

Pro-dynorphin peptides are found in the same neurons throughout rat brain: immunocytochemical study.

It is known that the opioid peptide dynorphin A has a broad distribution throughout the neuraxis. Recent biochemical studies have extended the sequence of dynorphin A by 15 amino acids to include another [Leu]enkephalin-containing peptide known as dynorphin B. These sequence data have been validated by the elucidation of the structure of the hypothalamic mRNA coding for alpha- and beta-neo-endorphin, dynorphin A, and dynorphin B. Using specific antisera directed against each of the three opioid peptides, we have studied their cellular distribution in rat brain. Their distribution patterns are extremely similar, if not identical. Furthermore, all three peptide immunoreactivities can be localized to the same cells in five nuclear groups throughout the brainstem--the supraoptic nucleus, the paraventricular nucleus, a group of cells in the lateral hypothalamic area, the nucleus parabrachialis, and the nucleus tractus solitarius. The sequence of a common precursor for dynorphin A, B, and alpha- and beta-neo-endorphin was deduced from hypothalamic mRNA. The ability to localize all three peptides together within cells in widely placed nuclei strongly supports the use of the same biosynthetic precursor for the neo-endorphin and dynorphin peptides in other parts of the central nervous system as well.

Animals↗
PubMed1983

Telencephalic enkephalinergic systems in the rat brain.

The comparative distribution of Leu-enkephalin and an enkephalin precursor fragment, BAM-22P, was studied in the rat telencephalon using immunocytochemical procedures. Although the enkephalins have previously been localized to telencephalic neurons, the use of high doses of colchicine in the present study has permitted the visualization of widespread enkephalin-containing systems in cortical-limbic regions. Rats were treated intraventricularly with colchicine (300 to 400 micrograms) to enhance the visualization of neuronal perikarya. Leu-enkephalin immunoreactivity was noted in perikarya as well as processes of neurons in many telencephalic regions including the olfactory bulb, parolfactory areas, olfactory tubercle, basal ganglia, nucleus accumbens, septal nuclei, amygdala, hippocampal formation, and several paleocortical regions such as the piriform, entorhinal, and cingulate cortex, as well as regions of the frontal, parietal, and occipital neocortex. In the majority of regions investigated, analysis of sections adjacent to those processed for Leu-enkephalin histochemistry showed BAM-22P immunoreactivity to be localized to perikarya and processes in the same region. These results suggest that brain enkephalin-positive neurons may possess mechanisms for enkephalin biosynthesis similar to those found in adrenal medullary enkephalin cells.

Animals↗
PubMed1982

Comparison of the distribution of dynorphin systems and enkephalin systems in brain.

A study of the anatomical distribution of the endogenous opioid dynorphin in rat brain showed that the peptide is localized in a widespread system with multiple cell groups and projections. This network is revealed by the use of multiple antiserums against dynorphin and can be distinguished from the system containing methionine-enkephalin and leucine-enkephalin, which is mapped by the use of antiserums against the enkephalins and biosynthetically related peptides in the adrenal. It thus appears that the brain contains at least three separate opioid neuronal networks: an enkephalin family with components similar to those found in the adrenal, a beta-endorphin family, and a dynorphin family.

Animals↗
PubMed1982

The carboxy terminus of the precursor to vasopressin and neurophysin: immunocytochemistry in rat brain.

A pituitary glycopeptide whose amino acid sequence was previously identified has now been recognized as the final portion of the precursor to arginine vasopressin and its associated neurophysin. Immunocytochemical techniques with antiserums against this 39 amino acid peptide and vasopressin were used to study their distribution in the rat central nervous system. The peptide is located in vasopressin-synthesizing cells in the neurosecretory magnocellular nuclei. Positively stained fibers project from the magnocellular nuclei through the median eminence to the posterior pituitary. Studies of the homozygous Brattleboro rat, which is known to be deficient in the production of vasopressin and its related neurophysin, also show the absence of immunoreactivity to this peptide. These immunocytochemical data strongly indicate that the peptide is synthesized with vasopressin.

Amino Acid Sequence↗
PubMed1982

Dynorphin and vasopressin: common localization in magnocellular neurons.

The opioid peptide dynorphin is widely distributed in neuronal tissue of rats. By immunocytochemical methods, it was shown previously that dynorphin-like immunoreactivity is present in the posterior pituitary and the cells of the hypothalamic neurosecretory magnocellular nuclei which also are responsible for the synthesis of oxytocin, vasopressin, and their neurophysins. By using an affinity-purified antiserum to the non-enkephalin part of the dynorphin molecule it has now been demonstrated that dynorphin and vasopressin occur in the same hypothalamic cells of rats, whereas dynorphin and oxytocin occur in separate cells. Homozygous Brattleboro rats (deficient in vasopressin) have magnocellular neurons that contain dynorphin separate from oxytocin. Thus dynorphin and vasopressin, although they occur in the same cells, appear to be under separate genetic control and presumably arise from different precursors.

Animals↗
PubMed1981

Opiate binding properties of naturally occurring N- and C-terminus modified beta-endorphins.

Beta-endorphin is further processed within the pituitary and brain by either N-terminal acetylation, carboxy-terminal proteolysis, or both. These naturally occurring analogues are stored intracellularly and, in some tissues, represent the majority of beta-endorphin immunoreactivity detected by antisera. It is therefore critical to determine their relative potencies at the opiate receptor. This study demonstrates that cleavage of the C-terminus tetrapeptide brings about a 10-fold decrease in opiate binding potency of either camel or human beta-endorphin. N-Acetylation, on the other hand, causes over a thousand fold loss in opiate potency rendering the peptide effectively inactive. Since unmodified beta-endorphin is approximately equipotent at multiple opiate receptors, we tested for possible differential shifts towards mu or delta-type receptors which may result from the modification. Our results show no change in selectivity, but simply an overall loss of potency.

Amino Acid Sequence↗
PubMed1981

Dynorphin immunocytochemical localization in brain and peripheral nervous system: preliminary studies.

Using antisera specific for the opioid peptide dynorphin, we have carried out immunocytochemical studies of the distribution in rat brain and periphery. In the central nervous system, cells that stain positively for dynorphin are found in the supraoptic nucleus, with less-well-stained cells in the paraventricular nucleus of the hypothalamus. Few positive fibers were detected in brain, suggesting problems with fixation and preservation of antigenicity. In pituitary no staining was seen in the anterior and intermediate lobes but heavy staining was detected in the posterior lobe. In the guinea pig, adrenal chromaffin cells stained with dynorphin antisera. Staining of these cells could be blocked with excess of dynorphin-(1-13) or either enkephalin. Radioimmunoassays revealed a great excess of the enkephalins in the adrenal, suggesting cross competition between dynorphin antiserum and adrenal medullary enkephalin. Finally, the dynorphin antiserum stained a complex of fibers in guinea pig ileum. Staining of these fibers could be blocked by moderate amounts of enkephalin as well as by smaller amounts of dynorphin-(1-13). We conclude that in some places (brain and pituitary) dynorphin exists separately from leucine-enkephalin. In other parts of brain and in the periphery the relationship between dynorphin and the enkephalins is very complex and requires further study and improved antisera.

Animals↗
PubMed1981

The effects of naloxone in chronic schizophrenia.

In a placebo-controlled, double-blind crossover study of 14 male chronic schizophrenic patients, high doses of the opiate antagonist naloxone were given intravenously. Hallucinations measured on a verbal-report scale were significantly decreased after naloxone administration. The authors suggest that this apparent action of naloxone is mediated by central opiate receptors and that it may result from an interaction between central endorphin systems and central catecholaminergic neurons.

Adult↗
PubMed1980

Evidence for homologous actions of pro-opiocortin products.

alpha-Melanocyte-stimulating hormone (alpha-MSH), a modified fragment of adrenocorticotropic hormone, derives from the same biosynthetic route as beta-endorphin and is stored by the same arcuate neurons. Microinjection of alpha-melanocyte-stimulating hormone and several related peptides into the periaqueductal gray matter significantly reduced responsiveness to pain and had a behavioral profile similar to that produced by beta-endorphin.

Adrenocorticotropic Hormone↗
PubMed1980

beta-Endorphin and schizophrenia.

To study the effects of beta-endorphin in chronic schizophrenia, nine male patients participated in a double-blind crossover comparison of a single intravenous 20-mg injection of beta-endorphin and saline. Bolus injection of beta-endorphin from an albumin-coated syringe produced markedly higher plasma concentrations than did slow intravenous infusion from a non-albumin-coated syringe. Beta-endorphin intravenously injected in nine patients produced a statistically significant increase in serum prolactin levels. In one patient, both 10 mg of morphine sulfate and 20 mg of beta-endorphin produced similar increases in the alpha power of the EEG. In eight patients, beta-endorphin administration was associated with a statistically significant but not clinically obvious improvement in schizophrenic symptoms.

Adult↗