Activation of A(3) receptors by endogenous adenosine inhibits synaptic transmission during hypoxia in rat cortical neurons.

PURPOSE: The aim of our study was to characterize the influence of A(3) receptors on synaptic potentials (PSPs) in pyramidal cells from the rat cingulate cortex during hypoxia. METHODS: Intracellular recordings (n=49) were taken from slice preparations. PSPs were evoked by electrical stimulation. RESULTS: Hypoxia (95%N(2)-5%CO(2), 5 min) reduced the amplitude of the PSPs significantly. The effect was more pronounced in the presence of adenosine re-uptake inhibitor S-(p-nitrobenzyl)-6-thioguanosine (NBTG) and deaminase inhibitor erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA); the effect was completely reversed by bovine adenosine deaminase. Hypoxic inhibition induced after A(1) receptor blockade with 1,3-dipropyl-8-cyclopentylxanthine (DPCPX) in the presence of NBTG was completely reversed by the A(3) antagonist 9-chloro-2-(2-furanyl)-5-[(phenylacetyl)amino]-1,2,4-triazolo[1,5-c]quinazoline (MRS 1220), indicating the involvement of A(3) receptors in hypoxic PSP inhibition. This was confirmed by A(3) agonist N(6)-(3-iodobenzyl)-adenosine-5'-N-methylcarboxamide (IB-MECA) inhibiting PSPs. The effect of IB-MECA was blocked by the rat A(3) receptor-selective antagonist 3-propyl-6-ethyl-5-[(ethylthio)carbonyl]-2-phenyl-4-propyl-3-pyridinecarboxylate (MRS 1523) and was not observed in the presence of G-protein inhibitor guanosine-5'-O-2-thiodiphosphate (GDP-beta-S). CONCLUSION: We conclude that a high level of endogenous adenosine, which occurs during hypoxia, activates A(3) receptors. Their activation contributes to PSP inhibition by adenosine during hypoxia.

Effects of alpha 1-adrenoceptor blocker prazosin on microcirculation in terminal rabbit ileum.

The influence of the specific alpha 1-blocker prazosin on the microcirculation of the terminal ileum was examined in 10 rabbits. For this purpose an isotope clearance test was carried out by administering 133-Xenon solution into the intestinal wall before and after the intra-arterial injection of prazosin (1.0 mg) via the superior mesenteric artery. These experiments were supplemented by haemodynamic and thermographic measurements in a further group of 5 rabbits. Due to the systemic circulatory effect of prazosin, i.e. the drug-induced hypotension, the bowel segment exhibited, contrary to expectations, significantly delayed values for isotope elimination indicating a reduced local tissue clearance and blood supply. Thermographic observations also confirmed the impairment of mesenteric blood flow after prazosin. Therapeutic applicability of alpha 1-adrenoceptor blockers to treat intestinal circulatory disturbances in diseases of vascular genesis thus remains dubious.

[The effect of the alpha1-receptor blocker prazosin on the microcirculation in the terminal ileum of rabbits]. / Zur Wirkung des alpha1-Rezeptorenblockers Prazosin auf die Mikrozirkulation im terminalen Ileum des Kaninchens.

The effect of the specific alpha1-blocker prazosin (Adversuten) on the microcirculation in the region of the terminal ileum was examined on 10 rabbits. Before and after injection of prazosin into the superior mesenteric artery an isotope-clearance of a 133Xe-solution, applied into the intestinal wall, was performed. Because of the systemic blood pressure decreasing effect of prazosin the circulation of the examined part of the intestine was reduced in spite of the intended vasodilation of the intestinal vessels. The therapeutic applicability of alpha-blockers for intestinal diseases of vascular genesis remains questionable.