Journal
JOURNAL OF NEUROCHEMISTRY
Volume 98, Issue 2, Pages 616-628Publisher
WILEY
DOI: 10.1111/j.1471-4159.2006.03912.x
Keywords
adenosine receptors; caffeine; carotid body; carotid sinus nerve; catecholamines; hypoxia
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Caffeine, an unspecific antagonist of adenosine receptors, is commonly used to treat the apnea of prematurity. We have defined the effects of caffeine on the carotid body (CB) chemoreceptors, the main peripheral controllers of breathing, and identified the adenosine receptors involved. Caffeine inhibited basal (IC50, 210 mu M) and low intensity (PO2 approximate to 66 mm Hg/30 mM K+) stimulation-induced release of catecholamines from chemoreceptor cells in intact preparations of rat CB in vitro. Opposite to caffeine, 5'-(N-ethylcarboxamido)adenosine (NECA; an A(2) agonist) augmented basal and low-intensity hypoxia-induced release. 2-p-(2-Carboxyethyl)phenethyl-amino-5'-N-ethylcaboxamido-adenosine hydrochloride (CGS21680), 2-hexynyl-NECA (HE-NECA) and SCH58621 (A(2A) receptors agents) neither affected catecholamine release nor altered the caffeine effects. The 8-cycle-1,3-dipropylxanthine (DPCPX; an A(1)/A(2B) antagonist) and 8-(4-{[(4-cyanophenyl)carbamoylmethyl]-oxy}phenyl)-1,3-di(n-propyl)xanthine (MRS1754; an A(2B) antagonist) mimicking of caffeine indicated that caffeine effects are mediated by A(2B) receptors. Immunocytochemical A(2B) receptors were located in tyrosine hydroxylase positive chemoreceptor cells. Caffeine reduced by 52% the chemosensory discharges elicited by hypoxia in the carotid sinus nerve. Inhibition had two components with pharmacological analysis indicating that A(2A) and A(2B) receptors mediate, respectively, the low (17 x 10(-9) M) and high (160 x 10(-6) M) IC50 effects. It is concluded that endogenous adenosine, via presynaptic A(2B) and postsynaptic A(2A) receptors, can exert excitatory effects on the overall output of the rat CB chemoreceptors.
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