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The adenosine-receptor modulation of noradrenaline release was compared in prostatic and epididymal portions of rat vas deferens. In both portions, tritium overflow elicited by electrical stimulation (100 pulses/8 Hz) was reduced by the adenosine A(1) receptor agonist, N(6)-cyclopentyladenosine, and enhanced by the nonselective receptor agonist, 5'-N-ethylcarboxamidoadenosine, in the presence of the adenosine A(1) receptor antagonist, 1,3-dipropyl-8-cyclopentyl-1,3-dipropylxanthine (DPCPX; 20 and 100 nM). The adenosine A(2A) receptor agonist, 2-p-(2-carboxyethyl)phenethyl-amino-5'-N-ethylcarboxamidoadenosine, increased tritium overflow, but only in the epididymal portion. The enhancement caused by NECA was prevented by the adenosine A(2A) receptor antagonist, 4-(2-[7-amino-2-(2-furyl)[1,2,4]triazolo-[2,3-a][1,3,5]triazin-5-ylamino]ethyl)phenol (ZM 241385; 20 nM), in the epididymal and by the adenosine A(2B) receptor antagonist, alloxazine (1 microM), in the prostatic portion. Inhibition of adenosine uptake enhanced tritium overflow in both portions, an effect blocked by ZM 241385 in the epididymal and by alloxazine in the prostatic portion. The results indicate that adenosine exerts an adenosine A(1) receptor-mediated inhibition, in both portions, and facilitation mediated by adenosine A(2A) receptors in the epididymal and by A(2B) receptors in the prostatic portion.

The aim of this study was to characterize the intestinal absorption of thiamine, by investigating the hypothesis of an involvement of Organic Cation Transporter (OCT) family members in this process. [(3)H]-T(+) uptake was found to be: 1) time-dependent, 2) Na(+)- and Cl(-)-dependent, 3) pH-dependent, with uptake increasing with a decrease in extracellular pH and decreasing with a decrease in intracellular pH, 4) inhibited by amiloride, 5) inhibited by the thiamine structural analogues oxythiamine and amprolium, 6) inhibited by the unrelated organic cations MPP(+), clonidine, dopamine, serotonin, 7) inhibited by the OCT inhibitors decynium22 and progesterone. Moreover, the dependence of [(3)H]-T(+) uptake on phosphorylation/dephosphorylation mechanisms was also investigated and [(3)H]-T(+) uptake was found to be reduced by PKA activation and protein tyrosine phosphatase and alkaline phosphatase inhibition. In conclusion, our results are compatible with the possibility of thiamine being transported not only by ThTr1 and/or ThTr2, but also by members of the OCT family of transporters (most probably OCT1 and/or OCT3), thus sharing the same transporters with several other organic cations at the small intestinal level.

The role of angiotensin II receptors, bradykinin receptors and beta-adrenoceptors in the modulation of noradrenaline release and the influence of alpha(2)-autoinhibition in these effects was investigated in the mesenteric artery and vein. Rings of mesenteric vessels of male Wistar rats were labelled with [(3)H]noradrenaline and the effects of modulators on tritium overflow evoked by 100 pulses at 2 Hz (marked alpha(2)-autoinhibition) and by 20 pulses at 50 Hz or 100 pulses at 2 Hz plus yohimbine (1 mu M; reduced alpha(2)-autoinhibition) were evaluated. Angiotensin II and bradykinin enhanced noradrenaline release evoked by 100 pulses at 2 Hz, in a concentration-dependent manner, in both vessels. These effects were attenuated under conditions of reduced alpha(2)-autoinhibition. The attenuation was partially reversed by activation of adenosine A(1) receptors in both vessels and by activation of P2Y receptors in the vein. Isoprenaline and the selective beta(2)-adrenoceptor agonist formoterol enhanced tritium overflow independently of alpha(2)-autoinhibition in the vein. In the artery, the enhancement by formoterol was only observed under reduced alpha(2)-autoinhibition. Pharmacological characterization of the beta-adrenoceptors indicated that in the artery the effect of isoprenaline was mediated by the beta(1)-subtype under marked alpha(2)-autoinhibition and by the beta(2)-subtype under reduced alpha(2)-autoinhibition whereas in the vein the effect was independent of alpha(2)-autoinhibition. The results indicate that alpha(2)-autoinhibition is a key determinant of the magnitude of facilitation caused by angiotensin II and bradykinin in both types of mesenteric vessels and regulates the effects mediated by beta(1)-and beta(2)-adrenoceptors which co-exist in the artery.