Adenosine receptors in the vasculature: Physiology, pharmacology and therapeutic perspectives

• Type: Chapter or Part of a Book
• Date: 2014

Authors

Sousa, JB (Author) Other; Soares, AS (Author) Other; Fresco, P (Author) FFUP; Diniz, C (Author) FFUP

Book

Title: Adenosine Receptors: Pharmacology, Functions and Therapeutic Aspects

Pages: 37-75

ISBN: 9781634634717; 9781634634540

Indexing

Scopus - 1 Citation

Other information

Authenticus ID: P-00K-4C6

Abstract (EN): Adenosine is a ubiquitous adenine base purine that mediates diverse biological and physiological processes in the cardiovascular system, both in cardiac and vascular tissues. Adenosine was reported to be involved in smooth muscle contraction, neurotransmission/neuromodulation, immune response and inflammation, platelet aggregation and modulation of cardiac function. Adenosine availability, in the extracellular space, depends on its release from a variety of cell types, as a result of adenosine triphosphate (ATP) enzymatic breakdown of both intra- and extracellular adenine nucleotides and intracellular S-adenosylhomocysteine. Other important source of extracellular adenosine lies on the activity of nucleoside transporters, both equilibrative (ENT) and concentrative (CNT), particularly ENT1, ENT4 and CNT2. As such adenosine can reach concentrations able to activate adenosine receptors. Four adenosine receptor subtypes have been identified, A1, A2A, A2B and A3 receptors, and were found to trigger different signalling pathways and to present differential affinity requirements. Correlation between the ENT activity and adenosine receptor activation is also discussed focusing on the impact that changes or disruption of the interplay between these effectors may cause in the vascular physiology, namely by contributing to disease. All adenosine receptor subtypes have been identified in the vascular wall of many different arteries and veins. A brief overview of the current knowledge and of our research work will be integrated considering important aspects of the adenosine-vascular interaction with particular emphasis on adenosine receptor subtypes pharmacology in the three vascular layers, intima, media and adventitia, namely by explaining their individual contribution for vasoconstriction/vasodilation. Integration of these knowledge with the morphological features of arteries/veins, namely by evidencing how innervation may vary from dense to sparse (depending on vessel localization) or how smooth muscle cell layers of the media varies (depending on vessel type and/or localization) will also be discussed, clarifying the contribution of adenosine receptors to peripheral vascular resistance. In the last decade several new adenosine receptor ligands have been identified as having promising therapeutic activities but during clinical trials some of them have been discontinued due to side effects. Despite of this fact, a renewed interest in this research area is emerging and several new adenosine receptor ligands have been developed and are undergoing clinical trials for a broad range of indications such as neurodegenerative disorders, inflammation, wound healing, cardiac imaging, etc. In summary, in this chapter an overview of adenosine/adenosine receptors physiology and pharmacology in the vasculature is presented guiding the reader to new and putative therapeutic applications.

Language: English

Type (Professor's evaluation): Scientific