 |
Endacea, Inc. - Science
Purinoceptor-Based Technologies
Purinoceptors are extracellular proteins located on
a number of different cell types in the human body.
They are coupled to intracellular signaling pathways
and activation of these receptors produces a number
of different physiological and pathophysiological effects.
Professor Geoffrey Burnstock (Autonomic Neuroscience
Institute, Royal Free Hospital School of Medicine, London) put forth the purinoceptor
hypothesis in 1978. He described two classes of purinoceptors,
adenosine-sensitive (P1) and ATP-sensitive
(P2) receptors (see Figure below). Four human
P1purinoceptors referred to as adenosine
receptors (ARs) have been cloned, A1, A2a,
A2b, and A3. Activation of these
ARs produces the following effects:
- A1 ARs: slowing of heart, depression
of heart contractility, bronchoconstriction, renal
and pulmonary vasoconstriction, proinflammatory cellular
effects, angiogenesis, sleep induction, and antinociception.
- A2a ARs: vasodilation, inhibition of
platelet aggregation, pain at peripheral sites, and
anti-inflammatory cellular effects.
- A2b ARs: hydration of the airway; release of cytokines from human airway bronchial and smooth muscle cells and fibroblasts; anti-inflammatory cellular and bronchorelaxant effects; decrease endothelial permeability.
- A3 ARs: anti-inflammatory cellular effects.
For a thorough and up to date review of ARs, see Wilson CN, Mustafa SJ (eds.), Adenosine Receptors in Health and Disease, Handbook of Experimental Pharmacology 193, Springer-Verlag Berlin Heidelberg 2009.
Click
to Enlarge
In 1985, Professor Burnstock described two major classes
of ATP-sensitive P2 purinoceptors, P2X and P2Y. Seven P2X and eight P2Y purinoceptors have been cloned and characterized. Activation
of P2X purinoceptors produces the following
effects: vasoconstriction, platelet aggregation, contraction
of the urinary bladder and colon, nociception, release
of mediators from macrophages (which are important in
septic shock), and activation of immune cells to produce
cell death of target cells by apoptosis.
Multiple Unmet Medical Need Opportunities Utilizing
Patent Protected Purinoceptor-Based Technologies:
Endacea’s Proprietary Series of A1
Adenosine Receptor Antagonists, A New Class
of Anti-inflammatory Drugs
Activation of A1 ARs and P2X purinoceptors on a number of different cell types, including
airway epithelial and smooth muscle cells, endothelial cells, macrophages,
and immune cells produces bronchoconstriction, endothelial
cell damage, tissue edema, hemorrhage, inflammation
and death of immune cells and target cancer cells that
underlie a number of different medical conditions including:
- asthma, chronic obstructive pulmonary disease (COPD),
allergic rhinitis;
- septicemia;
- ischemia-reperfusion organ injury;
- fibrosis (e.g. airway remodeling of asthma; cirrhosis
of the liver);
- sclerosis (e.g. atherosclerosis);
- Alzheimer’s disease; and
- cancer
For a discussion of ARs in asthma and in inflammation see:
- Wilson CN, Nadeem A, Spina D, Brown R, Page CP, Mustafa SJ (2009). Adenosine receptors and asthma. In Wilson CN, Mustafa SJ (eds) Adenosine Receptors in Health and Disease, Handbook of Experimental Pharmacology, Springer-Verlag Berlin Heidelberg, 193, pp 329-362.
- Blackburn MR, Vance CO, Morschl E, Wilson CN (2009). Adenosine receptors and inflammation. In Wilson CN, Mustafa SJ (eds) Adenosine Receptors in Health and Disease, Handbook of Experimental Pharmacology, Springer-Verlag Berlin Heidelberg, 193, pp 215-269.
|
 |
