9- adenosine activity

Adenosine activates the atrial Ai-adenosine receptor, which opens the Ik Ado channel leading to... 

Trussel, L. O. and Jackson, M. B. Adenosine-activated potassium conductance in cultured striatal neurons. Proc. Natl Acad. Sci. U.S.A. 82 4857-4661,1985. 

Dipyridamole increases coronary blood circulation, increases oxygen flow to the myocardium, potentiates adenosine activity, and impedes its metabolization. It inhibits aggregation of thrombocytes, blocks phosphodiesterase, increases microcirculation, and inhibits the formation of thrombocytes. 

Adenosine Activates inward rectifier Ik blocks ICa Very brief, usually complete AV blockade Paroxysmal supraventricular tachycardias IV only duration 10-15 Toxicity Flushing, chest tightness, dizziness Interactions Minimal... 

Famini, G.R., Loumbev, V.P., Frykman, E.K. and Wilson, L.Y. (1998). Using Theoretical Descriptors in a Correlation Analysis of Adenosine Activity. Quant.Struct.-Act.Relat., 17, 558-564. 

T. Krieg, Q. Qin, E. C. McIntosh, M. V. Cohen and J. M. Downey, ACh and adenosine activate PI3-kinase in rabbit hearts through transactivation of receptor tyrosine kinases, Am J Physiol 283, H2322-H2330, (2002). 

Aymerich, I., Foufelle, F Ferre, P., Casado, F.J., and Pastor-Anglada, M. (2006) Extracellular adenosine activates AMP-dependent protein kinase (AMPK). Journal of Cell Science, 119 (Pt 8), 1612-1621. 

Adverse effects with dipyridamole thallium testing are minimal, the main adverse effects being chest pain (with or without ischemic changes on the ECG), headache, dizziness, and nausea. Adverse effects are related to the increased adenosine activity and can be ameliorated by xanthine compounds because they are direct competitive antagonists of adenosine. Caffeine products must be avoided for about 24 hours prior to the test. Adenosine is associated with a higher incidence of adverse effects (80% versus 50%), but these are very transient, and some studies have shown that patients prefer it over dipyridamole. Both agents are relatively contraindicated in patients with a history of bronchospasm. 

Trussel, L. and Jackson, M., Dependence of an adenosine-activated potassium current on a GTP-binding protein in mammalian central neurons, J. Neurosci, 7, 3306, 1987. 

Hypoxia also causes the release of adenosine from cardiac myocytes. Adenosine in a potent dilator of coronary arteries. It has been shown that adenosine activates K xp currents in single coronary artery smooth muscle cells (Dart and Standen, 1993, 1994). Activation of the K xp channel is also involved in the hypoxic vasodilation in the cerebral, renal (Loutzen-hiser and Parker, 1994), skeletal muscle, and cremaster muscle and cheek pouch circulations (see Nelson and Quayle, 1995). Activation of K xp channels in these vascular beds may be a direct consequence of hypoxia on a smooth muscle oxygen sensor, an effect of hypoxia on smooth muscle cell metabolism, or through the release of vasodilator metabolites like adenosine from surrounding tissue, similar to hypoxic coronary vasodilation. 

Caffeine Caffeine, a mild stimulant, is the most widely used psychoactive drug in the world. It is present in soft drinks, coffee, tea, cocoa, chocolate, and numerous prescription and over-the-counter drugs. It mildly increases NE and DA release and enhances neural activity in numerous brain areas. Caffeine is absorbed from the digestive tract and is distributed rapidly throughout all tissues and easily crosses the placental barrier see Chapter 27). Many of caffeine s effects are beheved to occur by means of competitive antagonism at adenosine receptors. Adenosine is a neuromodulator that influences a number of functions in the CNS see Chapters 12 and 27). The mild sedating effects that occur when adenosine activates particrrlar adenosine-receptor subtypes can be antagonized by caffeine. 

ANS I do not know. There are different types of adenosine receptors. We have no evidence that the receptors are involved, in the sense that the pharmacologists believe on the basis of studies with a variety of adenosine analogues. Many investigators use the level of adenylate cyclase activity as an index of adenosine activity. The effects that I have shown you are the physiological effects that do not involve changes in cycle AMP. Hence, it must be via a different mechanism. 

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