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Measurement of Cyclic Guanosine Monophosphate (cGMP) in Solid Tissues using Competitive Enzyme-Linked Immunosorbent Assay (ELISA)
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Protein kinase C regulates NO-cGMP pathway in muscarinic receptor activation by HIV+-IgA

M E Sales1, A J Español, L Sterin-Borda

  • 1Instituto de Oncologia Angel H. Roffo, Buenos Aires, Argentina.

International Journal of Molecular Medicine
|May 26, 1999
PubMed

Insights

Immunoglobulin A (IgA) from HIV patients binds to intestinal muscarinic acetylcholine receptors (mAChR). This binding influences signaling pathways, potentially impacting intestinal immunity and function in HIV infection.

Area of Science:

  • Gastroenterology
  • Immunology
  • Neurogastroenterology

Background:

  • HIV infection is associated with gastrointestinal complications.
  • The role of immunoglobulin A (IgA) in HIV-related intestinal pathology is not fully understood.
  • Muscarinic acetylcholine receptors (mAChR) play a role in regulating intestinal function.

Purpose of the Study:

  • To investigate the interaction between IgA from HIV-infected patients and intestinal mAChR.
  • To elucidate the signaling pathways triggered by this interaction.
  • To understand the potential implications for intestinal dysfunction in HIV/AIDS.

Main Methods:

  • Purification of IgA from HIV-infected patients.
  • Immunoblotting with radiolabeled ileal mAChR.
  • Analysis of signaling molecules including protein kinase C (PKC), nitric oxide synthase (NOS), and cyclic guanosine monophosphate (cGMP).

Main Results:

  • HIV-patient-derived IgA (HIV+-IgA) recognized a specific band corresponding to mAChR.
  • HIV+-IgA initiated mAChR-mediated signaling in the intestine.
  • HIV+-IgA modulated PKC, NOS activity, and cGMP production.
  • PKC activation by HIV+-IgA led to NOS inhibition and reduced nitric oxide (NO) levels.
  • HIV+-IgA stimulated cGMP production, potentially increasing ileal motility and fluid secretion.

Conclusions:

  • IgA from HIV-infected individuals directly interacts with intestinal mAChR.
  • This interaction triggers signaling cascades with dual effects: potential local immunosuppression via NO inhibition and enhanced intestinal motility/secretion via cGMP.
  • These findings offer insights into the mechanisms underlying intestinal damage in AIDS.

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