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Adenosine is known to stimulate chloride secretion by mouse jejunum. Whereas the receptor on the basolateral side is believed to be A2B, the receptor involved in the luminal effect of adenosine has not been identified. We found that jejuna expressed mRNA for all adenosine receptor subtypes. In this study, we investigated the stimulation of chloride secretion by adenosine in jejuna derived from mice lacking the adenosine receptors of A1 (A1R) and A2A (A2AR) or control littermates. The jejunal epithelium was mounted in a Ussing chamber, and a new method on the basis of impedance analysis was used to calculate the short-circuit current (Isc) values. Chloride secretion was assessed by the Isc after inhibition of the sodium-glucose cotransporter by adding phloridzin to the apical bathing solution. The effect of apical adenosine on chloride secretion was lost in jejuna from mice lacking the A1R. There was no difference in the response to basolaterally applied adenosine or to apical forskolin. Furthermore, in jejuna from control mice, the effect of apical adenosine was also abolished in the presence of 8-cyclopentyl-1,3-dipropylxanthine, a specific A1R antagonist. Responses to adenosine were identical in jejuna from control and A2AR knockout mice. This study demonstrates that A1R (and not A2AR) mediates the enhancement of chloride secretion induced by luminal adenosine in mice jejunum. [ABSTRACT FROM AUTHOR]

Abstract The adenosine receptor agonist 2-[p-(2-carboxyethyl)phenylethylamino]-5'-N-ethylcarboxamidoadenosine (CGS 21680) is generally considered to be a selective adenosine A2A receptor ligand. However, the compound has previously been shown to exhibit binding characteristics that are not compatible with adenosine A2A receptor binding, at least in brain regions other than the striatum. We have examined binding of [³H]CGS 21680 and of antagonist radioligands with high selectivity for adenosine A1 or A2A receptors to hippocampus and striatum of mice lacking either adenosine A1 (A1R(-/-)) or A2A (A2AR(-/-)) receptors. Both receptor autoradiography and membrane binding techniques were used for this purpose and gave similar results. There were no significant changes in the binding of the A1 receptor antagonist [³H]DPCPX in mice lacking A2A receptors, or in the binding of the A2A receptor antagonists [³H]SCH 58261 and [³H]ZM 241385 in mice lacking A1 receptors. Furthermore, [³H]CGS 21680 binding in striatum was abolished in the A2AR(-/-), and essentially unaffected in striatum from mice lacking A1 receptors. In hippocampus, however, binding of [³H] CGS 21680 remained in the A2AR(-/-), whereas binding was virtually abolished in the A1R(-/-). There were no adaptive alterations in A2A receptor expression in this region in A1R(-/-) mice. Thus, most of the [³H]CGS 21680 binding in hippocampus is dependent on the presence of adenosine A1 receptors, but not on A2A receptors, indicating a novel binding site or novel binding mode. [ABSTRACT FROM AUTHOR]

In the present study we have investigated the neurotoxic effects of the exposure to a low dose (0.5 mg/kg/day) of methylmercury (MeHg) on the developing nervous system. Pregnant rats were treated with MeHg from day 7 of pregnancy to day 7 of lactation. At postnatal day 20 the offspring did not display prominent functional cerebellar alterations, as evaluated by the Rotarod performance. Motor activity (locomotion, rearing and motility) was tested in the 21-day-old rats after administration of apomorphine, an agonist of D1, D2, and D3 dopamine receptors. A low dose of apomorphine (0.1 mg/kg) induced a significantly stronger increase in motility and locomotion in MeHg-treated rats as compared to controls. The same effect was also observed in rats injected with 1 mg/kg apomorphine. No changes were observed in rearing at either doses of the dopamine receptor agonist. The data suggest that changes in dopaminergic transmission are induced by exposure to MeHg in early life. The expression of the striatal dopamine D1 and D2 receptors was examined by in situ hybridization in the striatum of the 21-day-old rats. The analysis did not reveal any significant changes at the mRNA level. Ligand autoradiography experiments showed a significant reduction in dopamine D2 receptor binding in the caudate putamen of MeHg-treated rats. Spatial learning ability was tested in 2-month-old rats using the Morris swim maze test. Changes in retention were shown in MeHg-treated rats, indicating that MeHg induced memory alterations. Taken together, these findings show that exposure to a very low dose of MeHg during development exerts neurotoxic effects on the dopaminergic system and that alterations of brain functions persist in adult life. [ABSTRACT FROM AUTHOR]