Ethylenediamine as a specific releasing agent of gamma-aminobutyric acid in rat striatal slices.

Following incubation with [14C]gamma-aminobutyric acid (GABA) or [3H]dopamine, slices of rat striatum were superfused with media containing 36 mM K+ or ethylenediamine (EDA), 1 or 5 mM. Both K+ and EDA induced a release being largely Ca2+-dependent, while the EDA-induced release was not. Whereas K+ also evoked a Ca2+-dependent release of [3H]dopamine, EDA evoked no release of dopamine.

Uptake and calcium-dependent release of ethylenediamine (1,2-diaminoethane) by rat brain slices.

The uptake of [14C]ethylenediamine into slices of rat brain and its subsequent evoked release have been studied. An active uptake process was demonstrated by comparing uptake at 37 and 4 degrees C. This uptake showed a Km of 1.

Cell-membrane receptors for purines. Review.

Purines are involved in many aspects of cell chemistry - intermediary metabolism, nucleic acid synthesis, and the supply of high-energy phosphates to various active transport systems. In addition, however, there appear to be specific receptor molecules located within the plasma membrane of some cells, which mediate changes of cell function in response to purines present in the extracellular fluid. It is the purpose of this review to summarize the kind of functions subserved by those receptors as well as the basic structural requirements for their activation.

Comparison of the effects of ethylenediamine analogues and gamma-aminobutyric acid on cortical and pallidal neurones.

1 The actions of ethylenediamine (EDA) and structurally related compounds were investigated by microiontophoresis in Wistar rats. 2 EDA inhibited, via a bicuculline-sensitive mechanism, the spontaneous firing rate of all cortical and pallidal cells tested. 3 The results with the analogues suggest that two amine groups are required for this neuronal depressant action whereas a carboxyl grouping is not.

Actions of adenine dinucleotides on the vas deferens, guinea-pig taenia caeci and bladder.

Adenine dinucleotides such as beta-NAD, alpha-NAD, NADP, 3-aminopyridine adenine dinucleotide, flavin adenine dinucleotide, 3',5'-and 2',5'-adenylyladenosine mimicked the inhibitory effects of adenosine and adenine nucleotides on electrically evoked contractions of the rat and mouse isolated superfused vas deferens. The inhibitory effects were blocked by theophylline or adenosine deaminase, unaffected by the nucleotidase inhibitor alpha, beta-methylene ADP and enhanced by inhibition of adenosine deaminase. The inhibitory effects were associated with a release of purines from the vasa after preloading with [3H]adenosine.

Differential blockade of ATP, noradrenaline and electrically evoked contractions of the rat vas deferens by nifedipine.

Nifedipine has recently been found to block electrically induced contractions of the prostatic portion of the vas deferens. The present results show that nifedipine blocks contractile responses to ATP in the parallel with the nerve mediated response, whereas the rapid phasic contractile response to noradrenaline is unaffected. The slower, tonic contractions to noradrenaline are blocked most easily, when the nerve-mediated responses are unchanged.

The effects of morphine and methionine-enkephalin on the release of purines from cerebral cortex slices of rats and mice.

1 Slices of cerebral cortex from Wistar rats, TO mice or C57 mice were preincubated with [3H]-adenosine, and labelled purines were subsequently releases by electrical stimulation or by perfusing with ouabain, 100 micro M. 2 Electrically-evoked purine release was substantially reduced when the Ca2+ concentration in the medium was lowered from 2.4 to 0.

The effects of 4-aminopyridine on the isolated vas deferens and its effects on the inhibitory properties of adenosine, morphine, noradrenaline and gamma-aminobutyric acid.

1 Adenosine, adenosine 5'-triphosphate (ATP), morphine, noradrenaline, gamma-aminobutyric acid (GABA) phentolamine and amyl nitrite were used to inhibit electrically-evoked contractions of the isolated superfused vas deferens of the mouse. 2 The inhibitory effects of adenosine ATP, morphine, noradrenaline and GABA, which are thought to be due to presynaptic action, were reduced by perfusion with media containing 4-aminopyridine (4AP) or tetraethylammonium (TEA) ions. The inhibitory effects of phentolamine and amyl nitrite were unaffected by 4AP or TEA.

Theophylline does not affect morphine inhibition of the isolated vas deferens.

1 Adenosine and morphine both produced an inhibition of the electrically-evoked twitch of the isolated superfused vas deferens of the mouse. 2 Theophylline, 10 or 100 muM, reduced the inhibitory action of adenosine but did not change inhibition by morphine. 3 It is suggested that adenosine release is not a necessary prerequisite for morphine inhibition of transmitter release.

Iontophoretic studies on pallidal neurones and the projection from the subthalamic nucleus.

The predominant response of pallidal neurones to gamma-aminobutyric acid (GABA), glycine and dopamine when applied iontophoretically, was inhibition of firing rate. With dopamine some excitatory responses were observed, this never being the case with GABA or glycine. Picrotoxin reversibly blocked neuronal responses to GABA but not glycine in fourteen cases.

Chronic methylxanthine treatment in rats: a comparison of Wistar and Fischer 344 strains.

Caffeine, theophylline or aminophylline were administered chronically to rats of both sexes, in the weight range 30-245 g. Self-injurious behaviour was noted only rarely in Wistar rats allowed free access to food, but developed over 3 to 4 weeks in half of the animals given a restricted diet of about one third of the intake of control rats. Fischer rats showed self-injurious behaviour more readily, 87% of animals showing signs within 9 days even on an ad lib diet.

Neuronal responses to ethylenediamine: preferential blockade by bicuculline.

The effects of ethylenediamine have been compared with GABA using two systems: microiontophoretic application to rat neurones in vivo, and superfusion of rat sympathetic ganglia in vitro. Using both techniques ethylenediamine mimicked closely the responses to GABA, showing a potency of 0.044 relative to GABA = 1.

Phosphonate analogues of carboxylic acids as aminoacid antagonists on rat cortical neurones.

Phosphonate analogues of carboxylic acids have been tested as antagonists of excitatory aminoacids in rat cerebral cortex. (+/-)--2-Amino-7-phosphono-heptanoic acid and the (-)-D-isomer of the pentanoate derivative were more potent and selective antagonists of N-methyl-D-aspartate (NMDA) than compounds tested previously. The results support the view that a distinct population of receptors exists which are preferentially activated by NMDA.

Methylxanthines modulate adenosine release from slices of cerebral cortex.

Using slices of mouse or rat cerebral cortex incubated with [3H]adenosine or [3H]adenine and/or [14C]GABA we have examined factors affecting the release of these compounds, and especially the influence of methylxanthines. Although release of purines and GABA could be induced by ouabain (10(-4) M), or p-hydroxymercuribenzoate (5 x 10(-4) M) no release was produced by ethacrynic acid (10(-3) or 10(-4) M) phenytoin (10(-3) M), noradrenaline or SC 13504. Release is probably not therefore related to (Na+, K+) ATPase or Mg2+-ATPase inhibition.

Activation of brown adipose tissue thermogenesis by the ventromedial hypothalamus.

It is well established that electrical stimulation of the ventromedial hypothalamus (VMH) causes a reduction in food intake, whereas electrolytic or chemical lesions in this area result in hyperphagia and obesity in the rat. This has led to the suggestion that either the ventromedial nucleus itself, or nerve fibres passing close by, are important in the control of food intake. However, obesity due to VMH lesions occurs in weanling rats in the absence of hyperphagia and can develop in adult rats pair-fed with controls, indicating that destruction of this area also causes an increased metabolic efficiency (that is, a reduced energy expenditure).

4-Aminopyridine blockade of neuronal depressant responses to adenosine triphosphate.

1 Adenosine, adenosine monophosphate and adenosine triphosphate (ATP) depressed the firing rate of neurones in the rat cerebral cortex when applied by microinontophoresis. 2 4-Aminopyridine, also applied iontophoretically blocked the depressant effects of the purines, without affecting responses to gamma-aminobutyric acid (GABA). This blockade was effected against purine depressions of both spontaneous and glutamate-evoked activity, suggesting that the interaction occurred postsynaptically.

Neuronal (Na+,K+)-ATPase and the release of purines from mouse and rat cerebral cortex.

Slices of mouse or rat cerebral cortex were incubated with [3H]adenine or [3H]adenosine, and [14C]GABA. Purines and GABA could subsequently be released by ouabain. The release of purines previously shown to occur on restoring elevated K+ levels to normal was not mimicked by noradrenaline at concentrations which activate (Na+,K+)-ATPase.