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  • 1
    Publication Date: 1997-10-10
    Description: Substance P is released in the spinal cord in response to painful stimuli, but its role in nociceptive signaling remains unclear. When a conjugate of substance P and the ribosome-inactivating protein saporin was infused into the spinal cord, it was internalized and cytotoxic to lamina I spinal cord neurons that express the substance P receptor. This treatment left responses to mild noxious stimuli unchanged, but markedly attenuated responses to highly noxious stimuli and mechanical and thermal hyperalgesia. Thus, lamina I spinal cord neurons that express the substance P receptor play a pivotal role in the transmission of highly noxious stimuli and the maintenance of hyperalgesia.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mantyh, P W -- Rogers, S D -- Honore, P -- Allen, B J -- Ghilardi, J R -- Li, J -- Daughters, R S -- Lappi, D A -- Wiley, R G -- Simone, D A -- MH56368/MH/NIMH NIH HHS/ -- NS23970/NS/NINDS NIH HHS/ -- NS31223/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 1997 Oct 10;278(5336):275-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Molecular Neurobiology Laboratory (151), Veterans Administration Medical Center, Minneapolis, MN 55417, USA. manty001@maroon.tc.umn.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9323204" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Capsaicin ; Cell Membrane/metabolism ; Cells, Cultured ; Fluorescent Antibody Technique ; Hyperalgesia/physiopathology/*therapy ; *Immunotoxins ; Injections, Spinal ; *N-Glycosyl Hydrolases ; Neurons/cytology/*metabolism ; Pain/physiopathology ; *Pain Management ; Pain Measurement ; Plant Proteins/metabolism/pharmacology ; Rats ; Rats, Sprague-Dawley ; Receptors, Neurokinin-1/biosynthesis/*metabolism ; Ribosome Inactivating Proteins, Type 1 ; Signal Transduction ; Spinal Cord/*cytology/metabolism ; Substance P/*metabolism/pharmacology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 1982-05-21
    Description: Certain toxic lectins, including ricin, are retrogradely transported along neuronal processes to the cell body where they inactivate ribosomes, resulting in neuronal death. This process of "suicide transport" suggests a powerful new experimental strategy for solving neurobiological problems.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wiley, R G -- Blessing, W W -- Reis, D J -- HL07378/HL/NHLBI NIH HHS/ -- HL18974/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 1982 May 21;216(4548):889-90.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6177039" target="_blank"〉PubMed〈/a〉
    Keywords: *Abrin ; Animals ; *Axonal Transport ; *Lectins ; Mice ; Nerve Degeneration/drug effects ; Neurons/*drug effects ; *Plant Lectins ; *Plant Proteins ; Retrograde Degeneration ; Ribosome Inactivating Proteins, Type 2 ; *Ricin
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 2019-07-13
    Description: Anti-dopamine beta-hydroxylase immunotoxin (DHIT) is an antibody-targeted noradrenergic lesioning tool comprised of a monoclonal antibody against the noradrenergic enzyme, dopamine beta-hydroxylase, conjugated to saporin, a ribosome-inactivating protein. Noradrenergic-neuron specificity and completeness and functionality of sympathectomy were assessed. Adult, male Sprague-Dawley rats were given 28.5, 85.7, 142 or 285 micrograms/kg DHIT i.v. Three days after injection, a 6% to 73% decrease in the neurons was found in the superior cervical ganglia of the animals. No loss of sensory, nodose and dorsal root ganglia, neurons was observed at the highest dose of DHIT. In contrast, the immunotoxin, 192-saporin (142 micrograms/kg), lesioned all three ganglia. To assess the sympathectomy, 2 wk after treatment (285 micrograms/kg), rats were anesthetized with urethane (1 g/kg) and cannulated in the femoral artery and vein. DHIT-treated animals' basal systolic blood pressure and heart rate were significantly lower than controls. Basal plasma norepinephrine levels were 41% lower in DHIT-treated animals than controls. Tyramine-stimulated release of norepinephrine in DHIT-treated rats was 27% of controls. Plasma epinephrine levels of DHIT animals were not reduced. DHIT-treated animals exhibited a 2-fold hypersensitivity to the alpha-adrenergic agonist phenylephrine. We conclude that DHIT selectively delivered saporin to noradrenergic neurons resulting in destruction of these neurons. Anti-dopamine beta-hydroxylase immunotoxin administration produces a rapid, irreversible sympathectomy.
    Keywords: Life Sciences (General)
    Type: The Journal of pharmacology and experimental therapeutics (ISSN 0022-3565); 275; 2; 1003-10
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  • 4
    Publication Date: 2019-07-13
    Description: Sympathectomy has been achieved by a variety of methods but each has its limitations. These include lack of tissue specificity, incomplete lesioning, and the age range of susceptibility to the lesioning. To circumvent these drawbacks, an immunotoxin was constructed using a monoclonal antibody against the noradrenergic specific enzyme dopamine beta-hydroxylase (D beta H) coupled via a disulfide bond to saporin, a ribosomal inactivating protein. Three days after intravenous injection of the anti-D beta H immunotoxin (50 micrograms) into adult Sprague-Dawley rats, 66% of neurons in the superior cervical ganglia were chromatolytic. Superior cervical ganglia neurons were poisoned in 1 day old and 1 week old (86% of neurons) neonatal rats following subcutaneous injection of 3.75 and 15 micrograms, respectively. The anti-D beta H immunotoxin will be a useful tool in the study of the peripheral noradrenergic system in adult and neonatal animals.
    Keywords: Life Sciences (General)
    Type: Brain research (ISSN 0006-8993); 666; 2; 195-200
    Format: text
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  • 5
    Publication Date: 1972-04-14
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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