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Biomedical subjects

T W Stone

Publications and source records attributed to T W Stone.

At least 235 records · Page 13Linked to original sources
PubMed1981

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. These findings support the view that neurally released ATP may contribute to contractile responses of the vas.

Adenosine Triphosphate↗
PubMed1981

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 = 1.0 in the ganglion. Bicuculline, but not strychnine, blocked ethylenediamine and GABA without affecting glycine, and strychnine blocked only glycine, in vivo. It was particularly clear from the in vitro experiments that bicuculline is about twice as effective an antagonist of ethylenediamine than of GABA.

Animals↗
PubMed1981

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.

2-Amino-5-phosphonovalerate↗
PubMed1981

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. At concentrations of 10(-3) and 10(-4) M, caffeine, theophylline, aminophylline and isobutyl-methylxanthine (IBMX) markedly depressed the release of purines evoked by ouabain. Non-xanthine inhibition of phosphodiesterase had much weaker though statistically significant effects. The methylxanthines had no significant effect on GABA release. It is suggested that the results can be explained on the basis of a positive feedback system in which released adenosine activates membranal adenylate cyclase, and the increased concentration of cyclic AMP which results form or origin of much of the adenosine released subsequently. However, we cannot exclude the existence of an intracellular receptor for methylxanthines which causes directly the inhibition of purine release.

1-Methyl-3-isobutylxanthine↗
PubMed1981

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). In normal rats, hyperphagia induced by feeding a highly palatable cafeteria diet is often accompanied by a large increase in heat production (diet-induced thermogenesis) which tends to prevent excessive weight gain and obesity. This diet-induced thermogenesis is due to sympathetic activation of brown adipose tissue (BAT) and we have now investigated the possibility that the VMH is involved in the activation of this process. We found that electrical stimulation of this area produced increased BAT thermogenesis, which suggests that the VMH exerts a dual influence in the regulation of energy balance--an inhibitory effect on energy intake and a stimulatory effect on thermogenesis and energy output.

Adipose Tissue, Brown↗
PubMed1981

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. It is suggested that Fischer rats treated with methylxanthines may provide a model of the Lesch-Nyhan syndrome. Behavioural observations made during the period of methylxanthine treatment suggest that an activation of both the dopamine and 5-hydroxytryptamine neurone systems may be produced. Further work will seek a relationship between these systems and self-injurious behaviour.

Aging↗
PubMed1981

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 0.1 mM. In both rats and mice, the electrically-evoked release was increased by morphine and methionine-enkephalin (Met-enkephalin), 10 micro M, and in rats and TO mice by morphine 1 micro M, both drug effects being prevented by naloxone. 3 Purine release evoked by ouabain was also increased by morphine 1 and 10 micro M, though not by Met-enkephalin, from slices of rat cortex. Ouabain-induced release from TO mice was reduced by morphine, and from C57 mice was unchanged. 4 The enhancement by morphine of electrically-evoked purine release may indicate that purines mediate some effects of morphine in the CNS.

Animals↗
PubMed1981

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. It is also suggested that the involvement of adenosine may follow activation only by opiate mu-receptors.

Adenosine↗
PubMed1981

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. 3 Quinidine, which like 4AP and TEA produced some increase to twitch height, did not reduce responses to the various agonists, indicating that an increased muscle contraction was not itself responsible for the reduced responses. 4 It is concluded that antagonism between 4AP and adenosine is not a specific interaction, as had been suggested, but probably reflects an interaction with Ca2+ requiring processes in the presynaptic terminal.

4-Aminopyridine↗
PubMed1981

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. Strychnine abolished glycine evoked inhibitions in seventeen cells while not affecting GABA responses. A number of cells were responsive to a stimulus delivered to the subthalamic nucleus (s.t.n.), an electrode array being used to establish the specificity of response to s.t.n. stimulation. In eight out of fourteen cases there was a reduction of 40% or more in the inhibitory responses following stimulation, with picrotoxin applied iontophoretically. Strychnine, conversely, had no effect on the synaptically evoked inhibition at doses that exceeded those required to antagonize iontophoretically applied glycine. Similarly, fluphenazine and naloxone administered iontophoretically or intraperitoneally (I.P.) had no effect on eight cells. The results indicate the existence of a 'GABA-ergic' link in the projection from the subthalamic nucleus to the globus pallidus, though other transmitters, but not glycine or dopamine, may contribute to the observed synaptic responses.

Animals↗
PubMed1980

The action of adenosine on noradrenergic neuronal inhibition induced by stimulation of locus coeruleus.

Stimulation of locus coeruleus (LC) has been used to induce a noradrenergic inhibition of neurones in the rat cerebral cortex. The local application of adenosine or adenosine monophosphate by microiontophoresis in the cortex was found to produce a reduction of the evoked inhibition if the purine application was begun 20 sec before LC stimulation, but an enhancement of the inhibition if applied up to 35 sec after the LC stimulation. GABA increased the duration of LC inhibition irrespective of time of application. Adenosine and GABA showed no mutual potentiation, but norepinephrine increased the size of responses to both iontophoretic adenosine and GABA. The adenosine-norepinephrine interaction was synergistic, irrespective of the order of application. It is concluded that adenosine may act both presynaptically to inhibit, and postsynaptically to enhance the effects of noradrenergic neurone activation, the dominant effect observed depending on the temporal relationship between LC activation and adenosine application.

Adenosine↗