title: HIV, opiates, and enteric neuron dysfunction.
abstract: Human immune deficient virus (HIV) is an immunosuppressive virus that targets CD4(+) T-lymphocytes. HIV infections cause increased susceptibility to opportunistic infections and cancer. HIV infection can also alter central nervous system (CNS) function causing cognitive impairment. HIV does not infect neurons but it does infect astrocytes and microglia in the CNS. HIV can also infect enteric glia initiating an intestinal inflammatory response which causes enteric neural injury and gut dysfunction. Part of the inflammatory response is HIV induced production of proteins including, Transactivator of transcription (Tat) which contribute to neuronal injury after release from HIV infected glial cells. A risk factor for HIV infection is intravenous drug use with contaminated needles and chronic opiate use can exacerbate neural injury in the nervous system. While most research focuses on the actions of Tat and other HIV related proteins and opiates on the brain, recent data indicate that Tat can cause intestinal inflammation and disruption of enteric neuron function, including alteration of Na(+) channel activity and action potential generation. A paper published in this issue of Neurogastroenterology and Motility extends these findings by identifying an interaction between Tat and morphine on enteric neuron Na(+) channels and on intestinal motility in vivo using a Tat expressing transgenic mouse model. These new data show that Tat protein can enhance the inhibitory actions of morphine on action potential generation and propulsive motility. These findings are important to our understanding of how HIV causes diarrhea in infected patients and for the use of opioid drugs to treat HIV-induced diarrhea.
authors: Neuroscience Program and the Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI, USA.
authors: J J
authors: JJ
authors: Galligan
mesh_terms: D000818:Animals; D003967:Diarrhea / Q000821:virology; D017615:Enteric Nervous System / Q000503:physiopathology / Q000821:virology*; D015658:HIV Infections / Q000150:complications*; D006801:Humans; D009020:Morphine / Q000009:adverse effects*; D009457:Neuroglia / Q000821:virology*; D009474:Neurons / Q000821:virology*; D015222:Sodium Channels / Q000378:metabolism; D054321:rev Gene Products, Human Immunodeficiency Virus / Q000378:metabolism
chemical_list: D015222:Sodium Channels; D054321:rev Gene Products, Human Immunodeficiency Virus; D009020:Morphine
keywords: Tat; diarrhea; enteric nervous system; enteric neuropathy; sodium channels