Metabolism of [14C]adenine and derivatives by cerebral tissues, superfused and electrically stimulated

Abstract

1. Uptake of [(14)C]adenine and [(14)C]adenosine from surrounding fluids to guinea-pig cerebral tissues was measured during incubation in vitro. Output of (14)C-labelled compounds from the loaded tissues to superfusion fluids occurred on continued incubation, at about 0.2% of the tissue's content/min, and this rate was increased about fourfold by electrical excitation of the tissue. 2. The compounds released from the tissue to superfusion fluids included adenine, adenosine, inosine and hypoxanthine with small amounts of nucleotides. Output of all these compounds, except adenine, increased on excitation. Media depleted of oxygen or glucose also increased the output of (14)C-labelled derivatives from [(14)C]adenine-loaded tissues, and this augmented output was further increased by electrical stimulation. 3. [(14)C]Adenosine was found as the main product from [(14)C]ATP when this was added at low concentrations to fluids superfusing cerebral tissue. Metabolic and neurohumoural explanations of the liberation and action of adenosine derivatives in the tissue are discussed.

The Antiepileptic Potential of Nucleosides

“…During bicuculline-, kainic-acid-, PTZ-and electroshockinduced seizures and 3-AP-induced epilepsy [112,372,[385][386][387][388], as well as electrical or chemical depolarization [389], the level of the Ado metabolites Ino and/or Hyp were also increased. It has been demonstrated that Ino (i) increased the latency to PTZ-induced seizures [118,390], (ii) antagonized caffeine-induced seizures [391], (iii) has a role in the electroshock-induced increase in the threshold to PTZ-induced seizures [387], (iv) had an anticonvulsant effect on QA-induced seizures [392] and (v) raised the threshold of seizures induced by PTZ, bicuculline and picrotoxin [58] (Table 4).…”

Effects of neutrophil elastase and other proteases on porcine aortic endothelial prostaglandin I2 production, adenine nucleotide release, and responses to vasoactive agents.

“…Basal release of 3H-nucleotides from unstimulated cell columns was <0.05% per min; this rose to a maximum of 0.9% per min after 100 jg/ml trypsin and 6.4% per min after 30 ,ug/ml elastase. These values were obtained by chromatography of samples using a solvent system (26) When cells were challenged a second time with ATP (100 AM) 20-40 min after the first challenge, the stimulation of PGI2 production was similar to the initial response (96.0±1.7%, n = 5). Since the proteases tested had variable effects on PGI2 production and on purine release, the effects of exposure to these proteases on subsequent PG12 responses to ATP were studied.…”

Interstitial Fluid Adenosine and Sagittal Sinus Blood Flow during Bicuculline-Seizures in Newborn Piglets

“…in tissue adenosine content observed in response to chemical seizures or elec trical stimulation (Pull and McIlwain, 1972;Rubio et al, 1975;Schultz and Lowenstein, 1978;Schrader et al, 1980;Winn et al, 1980). Bicucul line seizures in rats produced a 4.6-fold increase in brain adenosine content (Winn et al, 1980).…”