Abstract

The sites and mechanisms of cocaine induced cardiorespiratory failure are unknown. Both cocaine and pro-cocaine produce apneusis at the caudal ventrolateral medulla (CVLM). Pre-treatment of the CVLM with the anti- cholinesterase physostigmine (PHYS) inhibits cocaine-induced apneusis (CIA).
The aims of this application are to evaluate the effects of PHYS pre-treatment on pro-cocaine induced apneusis. To elucidate the mechanism of action of PHYS and to study excitatory amino acid (EAA) implications in CIA. Acetylcholinesterase hydrolysis of neuropeptides and apneusis after EAA blockade suggest involvement of substance P, opiates and EAA in CIA. Studies will be performed on the cholinomimetic property of PHYS by pre- treatment of the CVLM with PHYS + atropine and/or PHYS + hexamethonium prior to cocaine. Substance P, opiates, and agonists/antagonists of EAA receptors will also be evaluated for their ability to inhibit CIA. Experiments will be carried out in urethane anesthetized (2.0g/kg) cats. Drugs will be applied topically to the CVLM using small filter paper pledgets (5-ul). Tidal volume (VT), respiratory frequency (f), minute ventilation (VE), heart rate, systolic, diastolic and mean arterial pressures will be monitored. Statistical significance of differences, with and without pre-treatments, will be determined by ANOVA. Results will provide new knowledge about PHYS counter-action of CIA and EAA mechanisms in cocaine-induced cardiorespiratory failure.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Minority Biomedical Research Support - MBRS (S06)
Project #
3S06GM008016-29S2
Application #
6316639
Study Section
Project Start
1999-08-01
Project End
2000-07-31
Budget Start
1998-10-01
Budget End
1999-09-30
Support Year
29
Fiscal Year
2000
Total Cost
$176,450
Indirect Cost

  Institution

Name
Howard University
Department
Type
DUNS #
056282296
City
Washington
State
DC
Country
United States
Zip Code
20059

  Publications

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Johnston, Henry Richard; Hu, Yi-Juan; Gao, Jingjing et al. (2017) Identifying tagging SNPs for African specific genetic variation from the African Diaspora Genome. Sci Rep 7:46398
Kessler, Michael D; Yerges-Armstrong, Laura; Taub, Margaret A et al. (2016) Challenges and disparities in the application of personalized genomic medicine to populations with African ancestry. Nat Commun 7:12521
Liu, Ching-Ti; Raghavan, Sridharan; Maruthur, Nisa et al. (2016) Trans-ethnic Meta-analysis and Functional Annotation Illuminates the Genetic Architecture of Fasting Glucose and Insulin. Am J Hum Genet 99:56-75
Rand, Kristin A; Rohland, Nadin; Tandon, Arti et al. (2016) Whole-exome sequencing of over 4100 men of African ancestry and prostate cancer risk. Hum Mol Genet 25:371-81
Mathias, Rasika Ann; Taub, Margaret A; Gignoux, Christopher R et al. (2016) A continuum of admixture in the Western Hemisphere revealed by the African Diaspora genome. Nat Commun 7:12522
Ehret, Georg B (see original citation for additional authors) (2016) The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals. Nat Genet 48:1171-1184
Kurian, P; Dunston, G; Lindesay, J (2016) How quantum entanglement in DNA synchronizes double-strand breakage by type II restriction endonucleases. J Theor Biol 391:102-12
Ogunjirin, Adebowale E; Fortunak, Joseph M; Brown, LaVerne L et al. (2015) Competition, Selectivity and Efficacy of Analogs of A-84543 for Nicotinic Acetylcholine Receptors with Repositioning of Pyridine Nitrogen. Neurochem Res 40:2131-42
Winchester, Danyelle; Ricks-Santi, Luisel; Mason, Tshela et al. (2015) SPINK1 Promoter Variants Are Associated with Prostate Cancer Predisposing Alterations in Benign Prostatic Hyperplasia Patients. Anticancer Res 35:3811-9

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