Adenosine receptor, tolerance

The body responds to chronic presence of caffeine by increasing the number of adenosine receptor sites. This may be one of the reasons for the increased tolerance (and decreased efficacy as a stimulant) to caffeine in heavy coffee and tea drinkers. 

Blay J, White TD, Hoskin DW (1997) The extracellular fluid of solid carcinomas contains immunosuppressive concentrations of adenosine. Cancer Res 57(13) 2602-2605 Bruns RF (1980) Adenosine receptor activation in human fibroblasts nucleoside agonists and antagonists. Can J Physiol Pharmacol 58(6) 673-691 Cerniway RJ, Yang Z, Jacobson MA, Linden J, Matherne GP (2001) Targeted deletion of A3 adenosine receptors improves tolerance to ischemia-reperfusion injury in mouse myocardium. Am J Physiol 281(4) H1751-H1758... 

Cerniway RJ, Yang Z, Jacobson MA, Linden J, Matherne GP (2001) Targeted deletion of adenosine receptors improves tolerance to ischemia-reperfusion injury in mouse myocardium. Am J Physiol Heart Circ Physiol 281(4) H1751-H1758... 

Headrick JP, Willems L, Ashton KJ, Holmgren K, Peart J, Matherne GP (2003) Ischaemic tolerance in aged mouse myocardium the role of adenosine and effects of A( adenosine receptor overexpression. J Physiol 549(Pt 3) 823-833 Hein TW, Belardinelli L, Kuo L (1999) Adenosine A2a receptors mediate coronary microvascular dilation to adenosine role of nitric oxide and ATP-sensitive potassium channels. J Pharmacol Exp Ther 291(2) 655-664... 

In a reaction which demonstrates the functional group tolerance of the Sonogashira reaction, Cristalli and coworkers synthesized 143 as one of the number of derivatives of adenosine-5 -V-ethyluronamide [77]. This, along with several other derivatives was screened to assess potency in binding at the A2a over the Aj adenosine receptor. Compound 143 was found to be virtually non-selective for the A2a receptor (2.1 1), but possessed substantial vasodilating activity. 

The third mechanism, antagonism of the endogenous adenosine, is the most plausible mode of action because caffeine exerts its antagonism at micromolar levels. Its main metabolite, paraxanthine, is as potent as caffeine in blocking adenosine receptors. Caffeine is more potent at A2A receptors and less potent at A3 receptors compared to Aj and A2B receptors. An upregulation of adenosine receptor is the postulated biochemical mechanism of caffeine tolerance. 

Adenosine A2a receptors are localized to the indirect striatal output function and control motor behavior. Istradefylline is a novel adenosine A2a receptor antagonist, which demonstrated a clinically meaningful reduction in motor fluctuations in L-DOPA-treated patients with established motor complications, and is safe and well tolerated. 

DeSanty KP, Dar MS (2001b) Involvement of the cerebellar adenosine Al receptor in cannabinoid-induced motor incoordination in the acute and tolerant state in mice. Brain Res 905 178-187... 

Many researchers are working to understand why drugs like morphine and heroin are addictive. Studies with cells in culture have suggested one mechanism for morphine tolerance and addiction. Normally, when the cell receptors bind to enkephalins, this signals the cell to decrease the production of a chemical messenger called cyclic AMP, or simply cAMP. (This compound is very closely related to the nucleotide adenosine-5 -monophosphate.) The decrease in cAMP level helps to block pain and elevate one s mood. When morphine is apphed to these cells they initially respond by decreasing cAMP levels. However, with chronic use of morphine the cells become... 

The 1,4-dihydropyridines (DHPs) classes of privileged heterocyclic pharmacophores are well known for their calcium channel blocker activity. Other versatile biological profiles of 1,4-DHPs such as anticonvulsant activity, selective adenosine-A3 receptor antagonism, radioprotective activity, sirtuin activation, and inhibition, etc. have also been well known [186]. Conventionally, 1,4-DHPs could be accessed via the Hantzsch reaction, reduction of pyridines, addition to pyridines or cycloadditions, etc. As a facile and broadly tolerable protocol, the Hantzsch reaction consisting of cyclocondensation reaction of ethyl acetoacetate (2 equivalent) with an aldehyde and ammonia remains as a frequently employed tactic for the synthesis of 1,4-DHPs in a large number of areas such as stereoselective synthesis and green chemistry [187]. 

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