Purinergic signalling

Purinergic signalling refers to a system of cellular communication primarily involving the extracellular nucleotides adenosine triphosphate (ATP) and adenosine. This signalling mechanism plays a crucial role in various physiological processes, including neurotransmission, inflammation, and cardiovascular function. The concept of purinergic signalling was first proposed by Geoffrey Burnstock in 1972, revolutionizing the understanding of cellular communication.

Overview

Purinergic signalling involves the release of purine nucleotides and nucleosides, such as ATP and adenosine, from cells. These molecules act as extracellular messengers, binding to purinergic receptors on the surface of target cells. There are two main types of purinergic receptors: P1 receptors, which are adenosine receptors, and P2 receptors, which are ATP receptors. P2 receptors are further divided into P2X ionotropic receptors and P2Y metabotropic receptors.

Function

The function of purinergic signalling is diverse, affecting many physiological and pathological processes. In the nervous system, ATP serves as a neurotransmitter, mediating both excitatory and inhibitory synaptic transmission. In the immune system, purinergic signalling influences the migration, proliferation, and release of cytokines by immune cells. Additionally, it plays a significant role in cardiovascular function, including blood pressure regulation and heart rate, and in the mechanisms of pain and inflammation.

Purinergic Receptors

P1 Receptors

P1 receptors, or adenosine receptors, are a group of G protein-coupled receptors that are activated by adenosine. They are involved in various physiological processes, including inhibition of neurotransmitter release, vasodilation, and regulation of immune responses. There are four subtypes of P1 receptors: A1, A2A, A2B, and A3.

P2 Receptors

P2 receptors are activated by ATP and can be divided into P2X and P2Y receptors. P2X receptors are ligand-gated ion channels, while P2Y receptors are G protein-coupled receptors. These receptors are involved in numerous functions, such as muscle contraction, inflammation, and platelet aggregation.

Clinical Significance

Purinergic signalling has been implicated in a variety of diseases, including neurodegenerative diseases, cancer, and cardiovascular disorders. For example, alterations in purinergic signalling pathways have been observed in conditions such as Alzheimer's disease, Parkinson's disease, and chronic pain. Consequently, purinergic receptors are considered potential therapeutic targets for the treatment of these diseases.

Research and Therapeutic Applications

Research into purinergic signalling has led to the development of drugs targeting purinergic receptors. These include antagonists and agonists of P1 and P2 receptors, which have potential applications in treating conditions like pain, thrombosis, and inflammatory diseases.

Conclusion

Purinergic signalling is a fundamental aspect of cellular communication, with significant implications for health and disease. Ongoing research continues to uncover the complexities of this signalling system, offering new insights into its physiological roles and therapeutic potential.