Biomedical subjects

C Rialas

Publications and source records attributed to C Rialas.

6 recordsLinked to original sources

PubMed2002

Morphine 6 glucuronide stimulates nitric oxide release in mussel neural tissues: evidence for a morphine 6 glucuronide opiate receptor subtype.

We have previously demonstrated that Mytilus edulis pedal ganglia contain opiate alkaloids, i.e., morphine and morphine 6 glucuronide (M6G), as well as mu opiate receptor subtype fragments exhibiting high sequence similarity to those found in mammals. Now we demonstrate that M6G stimulates pedal ganglia constitutive nitric oxide (NO) synthase (cNOS)-derived NO release at identical concentrations and to similar peak levels as morphine. However, the classic opiate antagonist, naloxone, only blocked the ability of morphine to stimulate cNOS-derived NO release and not that of M6G. CTOP, a mu-specific antagonist, blocked the ability of M6G to induce cNOS-derived NO release as well as that of morphine, suggesting that a novel mu opiate receptor was present and selective toward M6G. In examining a receptor displacement analysis, both opiate alkaloids displaced [3H]-dihydromorphine binding to the mu opiate receptor subtype. However, morphine exhibited a twofold higher affinity, again suggesting that a novel mu opiate receptor may be present.

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PubMed2001

Morphine reduces herpes simplex virus-1 pathogenesis in the murine flank.

Here we investigate the effect of morphine on herpes simplex virus-1 (HSV-1) pathogenesis using a murine flank scarification model. Murine flank scarification with HSV-1 results in primary lesions at the site of inoculation within three days and lesions at secondary sites within four days. The lesions are scored based on lesion size. Applying 0.1 mM morphine to the skin one-day post inoculation tested the effect of morphine on the formation of the herpes lesion. On days three through five, mice treated with morphine developed lesions with scores half of that observed in untreated animals, however, skin viral titers on these days were equivalent. Further, 1.0 microM morphine did not effect the replication rate of HSV-1 in Vero cells. Taken together, these data suggest the morphine reduced HSV-1 pathogenesis by modifying the host response to HSV-1 infection and not by reducing viral replication rates.

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PubMed2000

Laminin-1 activates Cdc42 in the mechanism of laminin-1-mediated neurite outgrowth.

Here, we investigated the role of the small Rho GTPases Rac, Cdc42, and Rho in the mechanism of laminin-1-mediated neurite outgrowth in PC12 cells. PC12 cells were transfected with plasmids expressing wild-type and dominant-negative mutants of Rac (RacN17), Cdc42 (Cdc42N17), or Rho (RhoN19). Over 90% of the dominant-negative Rho- and Rac-transfected cells extended neurites when plated on laminin-1; however, none of the PC12 cells transfected with the dominant-negative Cdc42 mutant extended neurites. In cells cotransfected with plasmids expressing c-Jun N-terminal kinase and wild-type Cdc42, laminin-1 treatment stimulated detectable levels of c-Jun phosphorylation. Further, cotransfection with c-Jun N-terminal kinase and the dominant-negative Cdc42 mutant blocked laminin-1-mediated c-Jun phosphorylation. Transfection with either wild-type Rac or the dominant-negative Rac did not effect c-Jun phosphorylation. These data demonstrate that Cdc42 is activated by laminin-1 and that Cdc42 activation is required in the mechanism of laminin-1-mediated neurite outgrowth.

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PubMed2000

Endogenous morphine.

It is now well accepted that endogenous morphine is present in animals, both in invertebrates and vertebrates. It is a key signaling molecule that plays an important role in downregulating physiological responses, such as those in the immune system, including immune elements in the CNS. It has been demonstrated that a specific mu-opiate-receptor subtype, mu3, mediates these downregulatory effects through release of NO. This article examines morphine as an endogenous signaling molecule, in terms of its role in neural and immune regulation.

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PubMed2000

Heavy metals and neuroimmunomodulation in Mytilus edulis.

Immunocytes of mussels are the chief immune defense in these organisms. When an immunocyte becomes activated there is a conspicuous change in its morphology (i.e., from round to amoeboid) that can be quantified using image analytical tools. Active immunocytes will typically show larger perimeters and areas and a smaller shape factor. Immunocytes exposed to heavy metals become inactive (Cd, Hg and Pb) thus with smaller perimeters (e.g., Pb2+ 2 ppm: P = 69.72 micron) and areas (e.g., Pb2+ 2 ppm: A = 270 micron2) and larger shape factors (Pb2 2 ppm: SF = 0.65) than the unexposed control cells (alpha = 0.05). Xenobiotics may also interfere with neuroimmunomodulation processes such as nitric oxide (NO) release. The release of NO is catalyzed by a calcium dependent constitutive nitric oxide synthase (cNOS). Presently, we are exploring the effects of heavy metals and other pollutants on cNOS activity, measured as real time NO release, in immunocytes and pedal ganglia from M. edulis. Preliminary results suggest that immunocytes exposed to Pb2+ (5 ppm) cause NO release and does not seem to inhibit further NO release in the presence of morphine. The possible implications of NO mediated Pb2+ neurotoxicity are also explored.

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PubMed1998

Isolation and characterization of a leech neuropeptide in rat brains: coupling to nitric oxide release in leech, rat and human tissues.

The osmoregulator peptide (leech osmoregulatory factor, LORF; IPEPYVWD) was first found in the leech central nervous system (CNS). Given the fact that certain peptides can be found in mammals and invertebrates, e.g., opioid, we examined rat brains to determine if LORF was present. This peptide was found and isolated by successive reversed-phase HPLC purification steps and characterized by electrospray mass spectrometry measurement. It was sequenced by Edman degradation and quantified in different tissues by ELISA. Our results demonstrate the presence of LORF in the hypothalamus, thalamus, and striatum (6 pmol/mg of protein extract) and in other brain areas at lower levels. This octapeptide is also present in the rat duodenum and liver (10 to 14 pmol/mg) and at lower levels in heart, lung, pancreas and caudal spinal cord (< 5 pmol/mg). The testes, adrenals and kidneys have the lowest levels of all the tissues examined (ca. 0.5 pmol/mg of protein). Furthermore, we also demonstrate that LORF is coupled to nitric oxide (NO) release in leech CNS, rat hypothalamus and human saphenous vein in a manner which is inhibited by a nitric oxide synthase inhibitor as well as an antibody directed toward LORF. The study demonstrates that LORF, and its function in relation to NO release, has been conserved over more than 400 million years of evolution.

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