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Biomedical subjects

H Akil

Publications and source records attributed to H Akil.

At least 253 records · Page 14Linked to original sources
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

Nonopiate effects of dynorphin and des-Tyr-dynorphin.

Intracerebroventricular administration of dynorphin produced potent and long-lasting effects on motor function and the electroencephalogram in rats. In addition, local iontophoretic or pressure ejection of dynorphin consistently inhibited hippocampal unit activity. None of these effects were significantly affected by naloxone even at high doses. Moreover, a fragment of dynorphin that failed to displace any of a number of tritiated narcotics from rat brain homogenates produced similar effects on these physiological measures in vivo. On the basis of a variety of criteria for "opiate action," the results suggest that a second biologically active site within the dynorphin sequence is capable of quite potent but nonopiate effects.

Action Potentials↗
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

Induction of analgesia by central administration of ORG 2766, an analog of ACTH4--9.

Dose-dependent analgesia was produced by microinjection of ORG 2766 into the periaqueductal gray (PAG). This analgesia was found to be potent and long-lasting and occurred at doses which were equimolar to those necessary for morphine analgesia. The same doses failed to produce analgesia by the cerebroventricular route, suggesting that the PAG was the site of action of this effect. Naloxone failed to reduce the analgesia and morphine tolerant did not diminish the effect significantly. Additionally, ORG 2766 at concentrations up to 10 micrometer failed to inhibit binding of [3H]naloxone to brain opiate receptors in vitro. These results suggest a non-opiate mechanism of action and are discussed in terms of a proposed alpha-MSH or ACTH receptor.

Adrenocorticotropic Hormone↗
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

Binding of 3H-beta-endorphin to rat brain membranes: characterization of opiate properties and interaction with ACTH.

The binding of tritiated beta-endorphin (3H-beta-EP) to brain homogenates is described. This has been difficult to achieve due to the lack of availability of 3H-beta-EP and to technical difficulties associated with high non-specific binding of beta-EP. We now report that 3H-beta-EP binding is saturable, stereospecific, has high affinity and is inhibited by sodium. Its dissociation rate is ten-fold longer than that of naloxone. Its regional distribution exhibits interesting differences from naloxone and enkephalin binding. ACTH1-24 appears to displace it more effectively than it displaces 3H-naloxone. The results are discussed in terms of multiple transmitter systems and the multiple opiate receptor hypothesis.

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↗
PubMed1980

Behavioral effects of dynorphin 1-13 in the mouse and rat: initial observations.

Dynorphin is a recently identified, pharmacologically potent endogenous opioid peptide. Heretofore it has not been characterized for its behavioral effects. The effects of centrally infused dynorphin upon a variety of behaviors were therefore examined in mice and rats. The present findings point to a specific profile of behavioral activity. The peptide was active in facilitating feeding and grooming, but was inactive in modifying pain sensitivity and rearing behavior. Naloxone was generally ineffective in reversing behavioral effects. Dynorphin thus appears to have some opiate-like effects upon exogenous administration but may be rapidly broken down into a behaviorally potent non-opiate peptide fragment.

Animals↗