Effects of uric acid and caffeine on A1 adenosine receptor binding in developing rat brain.
Previous studies have demonstrated that elevated levels of serum uric acid or caffeine are associated with increased locomotor activity in rats and humans. Since uric acid and caffeine are structurally similar, it was hypothesized that these compounds alter locomotor activity through a common neural mechanism, specifically by acting as receptor antagonists at adenosine A1 binding sites. In vitro competition of caffeine and uric acid against the A1 agonist, [3H] cyclohexyladenosine ([3H]CHA), was conducted using homogenates of adult rat forebrain. Caffeine effectively competed for the A1 binding site as previously reported (IC50 = 107 microM), but uric acid failed to compete with [3H]CHA binding at concentrations within a relevant physiological range. Nevertheless, in vivo experiments indicated that chronic elevation of uric acid following allantoxanamide treatment of male rats on days 4-27 of life significantly decreased A1 receptor binding in the striatum, a region traditionally implicated in mammalian locomotion. In contrast, chronic caffeine treatment on days 4-27 of life caused an increase in A1 receptor binding in the cortex similar to increases reported previously in whole brain. These changes in A1 receptor binding following chronic elevation of uric acid or caffeine did not persist in rats that had been withdrawn from allantoxanamide or caffeine treatment for 14 days. Results from in vitro and in vivo experiments indicate that despite a similar molecular structure uric acid does not act by the same mechanism as caffeine to increase locomotor activity in rats.
Hunter
R E
RE
Department of Psychology, Tulane University, New Orleans, LA.
Barrera
C M
CM
Dohanich
G P
GP
Dunlap
W P
WP
D000241:Adenosine; D000375:Aging / Q000502:physiology*; D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002110:Caffeine / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D010094:Oxonic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011983:Receptors, Purinergic / Q000187:drug effects* / Q000378:metabolism; D013997:Time Factors; D014527:Uric Acid / Q000378:metabolism* / Q000494:pharmacology
D011983:Receptors, Purinergic; D014527:Uric Acid; D002110:Caffeine; D010094:Oxonic Acid; C018205:allantoxanamide; D000241:Adenosine