PHARM 203: Purines

Purines

Include adenosine, ADP, ATP, and methylxanthines (e.g. caffeine); involved in DNA/RNA synthesis, energy metabolism, and purinergic signaling.

Purinergic Signalling

Refers to signaling pathways using purines like ATP, ADP, and adenosine; regulates blood flow, platelet aggregation, neurotransmission, and immune responses.

Adenosine Nucleoside

Found in cytosol and body fluids; transported in and out of cells; has cardiovascular, CNS, and inflammatory effects.

Adenosine Cardiovascular Effects

Inhibits cardiac conduction, causes vasodilation (especially in coronaries), and inhibits platelet aggregation.

Adenosine CNS Effects

Generally inhibitory on neurons; caffeine (an adenosine antagonist) acts as a stimulant by blocking these effects.

Adenosine Inflammatory Effects

Acts via A1 receptors to promote mediator release from mast cells, increase mucus secretion, cause bronchoconstriction, and activate leukocytes.

A1 Receptor (A1R)

Adenosine receptor subtype (GPCR) mediating pro-inflammatory effects such as bronchoconstriction and mast cell activation.

A2A Receptor (A2AR)

Adenosine receptor subtype (GPCR) mediating anti-inflammatory effects.

Theophylline

Drug used in asthma treatment; works in part by blocking adenosine A1 receptors to prevent bronchoconstriction.

ADP (Adenosine Diphosphate)

Stored in vesicles and released by exocytosis; acts on P2Y receptors, especially P2Y12, to stimulate platelet aggregation.

P2Y12 Receptor

ADP receptor important in platelet aggregation; target for anti-platelet drugs like clopidogrel.

ATP (Adenosine Triphosphate)

Present in cells at high concentrations; acts via P2X receptors (ATP-gated cation channels); regulates vascular tone, insulin secretion, neurotransmission, and inflammation.

P2X Receptors

Ligand-gated ion channels activated by ATP; mediate cation influx leading to various physiological effects.

ATP and Vasodilation

ATP activates K+ channels to cause vasodilation and improve blood flow.

ATP and Insulin Secretion

ATP can stimulate insulin secretion from pancreatic β-cells.

ATP and Neurotransmission

Functions as a neurotransmitter in the peripheral nervous system.

ATP and Pain Transmission

Involved in nociception (pain transmission) through activation of P2X receptors.

ATP and Inflammation

Released from dead or dying cells; attracts neutrophils (chemotaxis) and contributes to inflammatory signaling.

Purinergic Receptors

Three main families: adenosine (A1–A3, GPCR), P2Y (P2Y1–14, GPCR), and P2X (ATP-gated cation channels).

Methylxanthines (e.g. Caffeine)

Adenosine receptor antagonists; increase alertness and act as CNS stimulants by blocking inhibitory adenosine signaling.

Adenosine

Endogenous nucleoside found in cytosol and body fluids; transported across cell membranes; acts via A1, A2A, and A3 receptors.

Adenosine Cardiovascular Effects

Inhibits cardiac conduction, causes vasodilation (especially in coronary vessels), and inhibits platelet aggregation.

Adenosine CNS Effects

Produces general inhibitory effects on neurons; caffeine (an adenosine antagonist) acts as a CNS stimulant by blocking these effects.

Adenosine Inflammatory Effects

Can have both pro- and anti-inflammatory actions depending on receptor subtype (A1R vs A2AR).

A1 Receptor (A1R)

G-protein coupled adenosine receptor that mediates pro-inflammatory responses; promotes mediator release from mast cells, enhances mucus secretion, causes bronchoconstriction, and activates leukocytes.

A2A Receptor (A2AR)

Adenosine receptor subtype with anti-inflammatory actions; suppresses immune cell activity and inflammatory mediator release.

A3 Receptor (A3R)

Less well characterized; involved in immune modulation and potential cytoprotective roles.

Theophylline

Drug used to treat asthma; acts by blocking adenosine A1 receptors, thereby preventing bronchoconstriction and mucus secretion.

Methylxanthines (e.g. Caffeine)

Adenosine receptor antagonists that increase alertness by reducing adenosine’s inhibitory effects in the CNS.

ADP (Adenosine Diphosphate)

Stored in intracellular vesicles and released by exocytosis; acts via P2Y receptors to mediate physiological effects.

P2Y Receptors (General)

G-protein coupled receptors (P2Y1–P2Y14) activated by ADP, ATP, and related nucleotides.

P2Y12 Receptor

ADP-activated receptor that promotes platelet aggregation; target of antiplatelet drugs like clopidogrel and ticagrelor.

ADP and Platelet Aggregation

ADP binds P2Y12 receptors on platelets to trigger aggregation and clot formation.

Antiplatelet Drugs (P2Y12 Blockers)

Medications that inhibit ADP binding to P2Y12 receptors to prevent thrombosis.

ATP (Adenosine Triphosphate)

High intracellular concentrations; acts mainly via P2X receptors; can be released through vesicles or channels.

P2X Receptors

Ligand-gated ion channels that open in response to ATP, allowing cation influx and producing fast signaling responses.

ATP and Vasodilation

ATP activates K+ channels via P2X receptor signaling to produce vasodilation and regulate blood flow.

ATP and Insulin Secretion

Stimulates insulin secretion from pancreatic β-cells through P2X receptor activation.

ATP and Neurotransmission

Functions as a neurotransmitter in the peripheral nervous system; mediates fast excitatory transmission.

ATP and Pain Transmission (Nociception)

Activates sensory neurons through P2X receptors to mediate pain signaling.

ATP and Inflammation

Released from dead or damaged cells; acts as a danger signal to recruit neutrophils and promote inflammation.