RECEPTOR PHARMACOLOGY IN ATOPIC DERMATITIS

Project: Research project

Description

Atopic dermatitis is a cutaneous inflammatory condition which usually
occurs in persons with a personal or family history of one or more atopic
diseases (i.e., asthma, allergic rhinitis or atopic dermatitis). Each of
these conditions may show evidence of immunologic and pharmacologic
dysfunction, but such aberrancies tend to be most pronounced in topic
dermatitis. This project is focused on the molecular basis of immunologic
and pharmacologic interactions. These studies have utilized mononuclear leukocytes which manifest a number
of immunologic abnormalities in atopic dermatitis. Our studies have also
demonstrated abormalities of cyclic nucleotide metabolism in patients'
cells. Cyclic AMP-phosphodiesterase activity is elevated and membrane
beta-adrenegic receptor binding is altered in atopic leukocytes. Similar
changes are induced in normal mononuclear leukocytes exposed to low
concentrations of histamine. It seems probable that these changes have a
common origin and identifying the basic molecular site of alteration may
lead to an understanding of pathomechanisms in atopic disease.
Histamine causes changes in mononuclear leukocytes and provides a useful
probe for delineating molecular defects in atopy and for clarifying the
effects of the inflammatory mediator on immune-associated cells. The
action of histamine on receptor binding, adenylate cyclase activity,
protein kinase activity and cyclic AMP turnover will be determined, thus
providing comprehensive assessment of various steps in the cyclic
nucleotide pathway. Comparisons with mononuclear leukocytes of patients
with atopic dermatitis will be made at each step to confirm the usefulness
of the histamine model. In addition, pertussis toxin, recently shown to
act on a specific subunit of the adenylate cyclase regulatory unit, will be
evaluated for similarities to hisatmine-induced and atopic cellular
abnormalities. This toxin has long been known to induce atopic
characeristics in animals. The above studies relate to the adenylate cyclase linked receptor system.
In addition, recent studies show a second major class of receptors linked
to inositol phospholipid metabolism. Preliminary evidence indicates
involvement of this pathway in atopic and histamine-treated normal
mononuclear leukoycytes. Further investigations of inositol phospholipid
metabolism will allow evaluation of abnormalities and relationships
with1the cyclic nucleotide system in atopic dermatitis.
StatusFinished
Effective start/end date9/1/798/31/88

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health

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Atopic Dermatitis
Mononuclear Leukocytes
Histamine
Pharmacology
Adenylyl Cyclases
Cyclic Nucleotides
Cyclic AMP
Histamine Receptors
Pertussis Toxin
Phosphoric Diester Hydrolases
Inositol
Phosphatidylinositols
Protein Kinases
Leukocytes
Asthma
Skin

ASJC

  • Medicine(all)
  • Immunology and Microbiology(all)