Adenosine neurotransmitter

Adenosine is produced by many tissues, mainly as a byproduct of ATP breakdown. It is released from neurons, glia and other cells, possibly through the operation of the membrane transport system. Its rate of production varies with the functional state of the tissue and it may play a role as an autocrine or paracrine mediator (e.g. controlling blood flow). The uptake of adenosine is blocked by dipyridamole, which has vasodilatory effects. The effects of adenosine are mediated by a group of G protein-coupled receptors (the Gi/o-coupled Ai- and A3 receptors, and the Gs-coupled A2a-/A2B receptors). Ai receptors can mediate vasoconstriction, block of cardiac atrioventricular conduction and reduction of force of contraction, bronchoconstriction, and inhibition of neurotransmitter release. A2 receptors mediate vasodilatation and are involved in the stimulation of nociceptive afferent neurons. A3 receptors mediate the release of mediators from mast cells. Methylxanthines (e.g. caffeine) function as antagonists of Ai and A2 receptors. Adenosine itself is used to terminate supraventricular tachycardia by intravenous bolus injection. 

Adenosine production in the synapse is not through vesicular release in response to nerve firing, as is the case for classical neurotransmitters. Rather, adenosine acts as a local autacoid, the release of which increases upon stress to an organ or tissue. Most cells in culture and in situ produce and release adenosine extracellularly. This... 

Unlike classical neurotransmitters, adenosine does not have a rapid synaptic uptake system (as for the biogenic amines), and its chemical inactivation system is not as rapid as for the transmitter acetylcholine, for example. Adenosine may be metabolized extracellularly and inactivated with respect to the ARs in a more general fashion by the widespread enzymes adenosine kinase (AK, to produce AMP) and adenosine deaminase (AD, to produce inosine). Both AMP and inosine are only weakly active at ARs, depending on the subtype. 

Caffeine binds to adenosine receptors in the brain, preventing adenosine from inducing sleep or opening blood vessels. Caffeine also increases levels of dopamine, the neurotransmitter associated with pleasure. This is the chemical mechanism for addiction. The response to adenosine competition causes increased adrenaline flow. 

The most promising mechanism of action, which may account for some of caffeine s potential ergogenic effects, involves its demonstrated ability as a competitive antagonist of the depressant effects of adenosine analogs in the central nervous system. Adenosine and its derivatives have been shown to inhibit neuronal electrical activity, the release of neurotransmitters, and to interfere with synaptic transmission.19-24 27... 

Dl-iike receptors activate the Gs transduction pathway, stimulating the production of adenylyl cyclase, which increases the formation of cyclic adenosine monophosphate (cAMP) and ultimately increases the activity of cAMP-dependent protein kinase (PKA). PKA activates DARPP-32 (dopamine and cyclic adenosine 3, 5 -monophosphate-regulated phosphoprotein, 32 kDa) via phosphorylation, permitting phospho-DARPP-32 to then inhibit protein phosphatase-1 (PP-1). The downstream effect of decreased PP-1 activity is an increase in the phosphorylation states of assorted downstream effector proteins regulating neurotransmitter... 

An unanswered question about adenosine is how this inhibitory neurotransmitter activates the ventrolateral preoptic area of the hypothalamus (VLPO), which contains a population of sleep-active neurons and is hypothesized to be... 

Caffeine The psychostimulant found in colfee, tea and a wide variety of carbonated soft drinks. Chemically related to the purine neurotransmitter adenosine, the drug blocks adenosine receptors in the nervous system. 

Cyclic AMP Stimulation or inhibition of the biosynthesis of the second messenger cyclic adenosine-S jS -monophosphate occurs through the activation of Gs or G protein-coupled neurotransmitter receptors, respectively. 

Purines such as ATP and adenosine play a central role in the energy metabolism of all life forms. This fact probably delayed recognition of other roles for purines as autocrine and paracrine substances and neurotransmitters. Today it is recognized that purines are released from neurons and other cells and that they produce widespread effects on multiple organ systems by binding to purinergic receptors located on the cell surface. The principal ligands for... 

Adenosine is not a classical neurotransmitter because it is not stored in neuronal synaptic granules or released in quanta. It is generally thought of as a neuromodulator that gains access to the extracellular space in part from the breakdown of extracellular adenine nucleotides and in part by translocation from the cytoplasm of cells by nucleoside transport proteins, particularly in stressed or ischemic tissues (Fig. 17-2C). Extracellular adenosine is rapidly removed in part by reuptake into cells and conversion to AMP by adenosine kinase and in part by degradation to inosine by adenosine deaminases. Adenosine deaminase is mainly cytosolic but it also occurs as a cell surface ectoenzyme. 

A1 adenosine receptors are inhibitory in the central nervous system. A receptors were originally characterized on the basis of their ability to inhibit adenylyl cyclase in adipose tissue. A number of other G-protein-mediated effectors of A receptors have subsequently been discovered these include activation of K+ channels, extensively characterized in striatal neurons [13], and inhibition of Ca2+ channels, extensively characterized in dorsal root ganglion cells [14]. Activation of A receptors has been shown to produce a species-dependent stimulation or inhibition of the phosphatidylinositol pathway in cerebral cortex. In other tissues, activation of A receptors results in synergistic activation of the phosphatidylinositol pathway in concert with Ca2+-mobilizing hormones or neurotransmitters [15]. The effectors of A adenosine receptors and other purinergic receptor subtypes are summarized in Table 17-2. 

Acetylcholine works with other neurotransmitters (i.e., cyclic guanylate monophosphate, cyclic adenosine monophosphate, vasoactive intestinal polypeptide) to produce penile arterial vasodilation and ultimately an erection. 

Alprostadil, or prostaglandin E1 stimulates adenyl cyclase to increase production of cyclic adenosine monophosphate, a neurotransmitter that ultimately enhances blood flow to and blood filling of the corpora. 

Adenosine A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. [NIH]... 

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