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Biomedical subjects

M E Newman

Publications and source records attributed to M E Newman.

At least 91 records · Page 5Linked to original sources
PubMed1989

Post-receptor-mediated increases in adenylate cyclase activity after chronic antidepressant treatment: relationship to receptor desensitization.

Administration to rats of chronic electroconvulsive shock (ECS) or chronic desipramine (DMI, 10 mg/kg daily i.p. for 3 weeks) did not affect either basal or forskolin-stimulated adenylate cyclase activity in membranes prepared from the caudate nucleus. In cerebellar membranes prepared from rats which had received chronic ECS, forskolin-stimulated activity was significantly increased compared to activity in sham- or single ECS treated rats. Forskolin-stimulated adenylate cyclase was increased in both hippocampal and cerebellar membranes from rats which received chronic DMI, compared to saline-treated animals. In cerebellar membranes, increases comparable to those with forskolin were also obtained with guanylyl-5'-imidodiphosphate (GppNHp) after both treatments, while with Mn2+ ions, either alone or in the additional presence of forskolin, the changes observed were similar to those previously reported in cortical membranes. A possible mechanism for these effects was investigated by studying antidepressant-induced and in vitro desensitization of the cyclic AMP response in slice preparations from the various brain areas. In slices from caudate nucleus, chronic DMI did not alter stimulation of cyclic AMP formation by either noradrenaline or forskolin, while in cerebellar slices the noradrenaline response was significantly reduced, and in hippocampal slices both responses were reduced (heterologous desensitization). In vitro incubation of cortical slices with noradrenaline also resulted in a reduction in the response to both agents. However, in membranes prepared from the desensitized cortical slices, there was no change in the degree of activation of adenylate cyclase by either NaF or forskolin. Thus, the increase in these activities, observed in certain brain areas after chronic antidepressant treatment may not necessarily be related to beta-adrenoceptor desensitization.

Adenylyl Cyclases↗
PubMed1989

Effects of chronic electroconvulsive shock on D1 and D2 dopamine receptor-mediated activity of adenylate cyclase in homogenates of striatum and limbic forebrain of rat.

Stimulation of adenylate cyclase by dopamine in homogenates of the striatum was unaltered in rats which had received either a single or a series of 10 electroconvulsive shock, compared to those which received sham treatment. In homogenates of the limbic forebrain, stimulation by both 100 microM dopamine and by 4 microM SKF 38393 was significantly increased after chronic electroconvulsive shock. The activity of D2 receptors, as measured by inhibition of forskolin-stimulated adenylate cyclase, in the presence of the D1 receptor antagonist SCH 23390, was unaltered by chronic electroconvulsive shock in either area of the brain. The selective effect of chronic electroconvulsive shock in increasing the activity of D1 receptors may account both for the increase, in dopamine-mediated behaviour, seen after chronic electroconvulsive shock and for the antiparkinsonian effects of this treatment.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1989

Modulation of second messenger function in rat brain by in vivo alteration of receptor sensitivity: relevance to the mechanism of action of electroconvulsive therapy and antidepressants.

1. The second messengers cyclic AMP and inositol triphosphate are the intracellular mediators for a number of neurotransmitters for which receptors exist on brain neurons. 2. Up- or down-regulation of these receptors in general produce corresponding changes in the associated second messenger systems. 3. Chronic administration of antidepressants including electroconvulsive shock to rats produces a number of changes in cerebral receptors, notably down-regulation of beta-adrenergic and serotonin 5-HT2 receptors and up-regulation of alpha-1 adrenergic receptors. 4. The changes in receptor number induced by such antidepressant treatments are in general accompanied by corresponding changes in the associated second messenger reactions. 5. Antidepressant administration has also been shown to induce increased post-receptor mediated adenylate cyclase activity in cortical membranes, and similar effects have also been reported in striatum after chronic administration of neuroleptics. The relevance of these effects to the mechanism of action of the drugs is discussed.

Animals↗
PubMed1988

Effects of lithium and desipramine administration on agonist-stimulated inositol phosphate accumulation in rat cerebral cortex.

The effects of acute lithium and chronic desipramine administration on the inositol phosphate responses of rat cerebral cortical slices to noradrenaline, carbachol and 5-hydroxytryptamine, were determined. Acute injection of lithium (4 meq/kg s.c. 24 hr before sacrifice) significantly increased the inositol-1-phosphate response to noradrenaline, while chronic administration of desipramine (10 mg/kg i.p. for 3 weeks) produced a smaller increase in this parameter. Chronic desipramine also decreased the serotonin responses in terms of all three inositol phosphates measured. No potentiative or additive interactions between the lithium and desipramine effects were observed.

Animals↗
PubMed1988

Chronic electroconvulsive shock and desimipramine reduce the degree of inhibition by 5-HT and carbachol of forskolin-stimulated adenylate cyclase in rat hippocampal membranes.

The degree of inhibition of forskolin-stimulated adenylate cyclase activity by 5-HT and by carbachol in hippocampal membranes was significantly reduced after administration of either chronic ECS (10 days) or desimipramine (10 mg/kg i.p. for 3 weeks). A single ECS had no effect on the 5-HT response and slightly augmented the carbachol response. These results parallel previous observations on the effects of ECS and antidepressants on behavioral responses to 5-HT1a agonists and on muscarinic receptor number, and indicate the possible involvement of these receptors in the mechanism of action of antidepressant drugs.

Adenylyl Cyclases↗
PubMed1987

Differential effects of chronic administration of desipramine on the cyclic AMP response in cortical slices and membranes in the rat.

Chronic administration of desipramine resulted in a significant decrease in the degree of stimulation of production of cyclic AMP by noradrenaline, isoproterenol and forskolin in slices of the cerebral cortex of the rat. In preparations of membranes from similarly treated animals, GppNHp- and forskolin-stimulated adenylate cyclase activity was increased, while isoproterenol-, manganese- and sodium fluoride-stimulated activity was unchanged. It is concluded that chronic administration of desipramine exerts effects on the adenylate cyclase system additional to its action on beta-adrenergic receptors, possibly by modifying the catalytic or guanyl nucleotide binding units of the enzyme.

Adenylyl Cyclases↗
PubMed1987

Effects of single and repeated electroconvulsive shock administration on inositol phosphate accumulation in rat brain slices.

Accumulation of inositol-1-phosphate after labeling with [3H]inositol and stimulation with noradrenaline, carbachol, and serotonin was measured in rat cortical, caudate nucleus, and hippocampal slices. The response to noradrenaline was significantly increased in cortical slices from animals that had received either a single electroconvulsive shock (ECS) or a series of 10 daily ECS but was unchanged in caudate nucleus or hippocampal slices. The response to carbachol, a muscarinic cholinergic agonist, was unchanged in cortical or caudate nucleus slices but was significantly reduced in hippocampal slices from animals that had received chronic ECS. The response to serotonin in cortical slices was not affected by the treatment. The results are correlated with changes in receptor number, which have been demonstrated to occur after administration of ECS.

Animals↗
PubMed1986

Electroconvulsive shock and cyclic AMP signal transduction: effects distal to the receptor.

Chronic electroconvulsive shock (ECS) induced a significant decrease in noradrenaline- and forskolin-stimulated cyclic AMP production in rat cortical slices, whereas a single ECS had a much smaller effect. In a cortical membrane preparation, adenylate cyclase activity in response to stimulation by forskolin, guanosine-5'-(beta,gamma-imido) triphosphate, and Mn2+ ions was significantly increased in membranes derived from rats that had received chronic ECS, but was either unchanged or reduced in membranes from rats that received a single treatment only. The results are interpreted in terms of changes occurring at components of the adenylate cyclase enzyme distal to the receptor.

Adenylyl Cyclases↗
PubMed1985

Vasopressin inhibition of cyclic AMP accumulation and effects on the learned response in inbred mouse strains.

The effects of a single injection of arginine vasopressin on the cyclic AMP responses of cerebral cortex slices to noradrenaline, forskolin and 2-chloro-adenosine were tested in six inbred mouse strains. The noradrenaline response was reduced in one strain and that to 2-Cl-adenosine in 2 strains. There was a positive correlation between the differences in the cyclic AMP response to 2-Cl-adenosine between control and AVP-treated mice and the differences in latencies during the extinction period of conditioned avoidance response learning.

2-Chloroadenosine↗
PubMed1985

Adenosine-homocysteine interactions in controlling cyclic AMP in rat brain cortical slices.

Preincubation of rat brain cortical slices with homocysteine resulted in a reduction of the cyclic AMP response to subsequently added noradrenaline or isoproterenol. There was no effect of homocysteine on the adenosine response, nor of added S-adenosyl homocysteine on any of the responses studied. The results are interpreted in terms of binding of endogenous adenosine by the enzyme S-adenosylhomocysteinase, and provide further evidence for the controlling role of adenosine on cerebral cyclic AMP production.

Adenosine↗
PubMed1985

Vasopressin inhibits cyclic AMP accumulation and adenylate cyclase activity in cerebral preparations.

Arginine-vasopressin (AVP) and lysine vasopressin (LVP) elicited a dose-dependent inhibition of noradrenaline-sensitive cyclic AMP accumulation in rat cerebral cortical slices, and of forskolin-stimulated adenylate cyclase activity in a rat cerebral cortical membrane preparation. In both cases LVP was more potent than AVP, and exerted half-maximal effects at concentrations similar to those found effective in binding studies on rat hippocampal membranes. In hippocampal slices, AVP did not affect cyclic AMP accumulation at low concentrations but potentiated the effect of noradrenaline at higher concentrations. In caudate membranes, AVP inhibited dopamine-stimulated adenylate cyclase with a similar dose-dependency to that seen for forskolin activation in cortex membranes.

Adenylyl Cyclase Inhibitors↗
PubMed1985

Effects of lithium in vitro on noradrenaline-induced cyclic AMP accumulation in rat cortical slices after reserpine-induced supersensitivity.

Lithium in vitro at concentrations of 1-2 mM and above inhibited cyclic AMP accumulation due to noradrenaline in cerebral cortical slices prepared from both control rats and rats rendered supersensitive for the noradrenaline response by intraperitoneal injection of reserpine. There was no difference in the concentration-dependence of lithium inhibition between control and reserpine-treated rats.

Animals↗
PubMed1985

Effects of vasopressin on noradrenaline-induced cyclic AMP accumulation in rat brain slices.

Addition of arginine vasopressin (AVP) or 1-desamino-8-D-arginine vasopressin (DDAVP) to rat cortical slices resulted in significant inhibition of the rise in cyclic AMP produced by incubation with 50 microM noradrenaline. A single injection of DDAVP (20 micrograms/rat) produced a reduced response to noradrenaline in derived cortex and caudate slices. In animals pretreated at day 5 of life with IP desipramine and intracisternal 6-hydroxydopamine (6-OHDA), both acute and chronic treatments with DDAVP resulted in a reduction in response in derived cortical, caudate and hippocampal slices. The 6-OHDA pretreated animals also showed reduced open-field behavioural activity after both acute and chronic DDAVP, while animals which were not pretreated responded to acute treatment only. The relationship between the effects of vasopressin on noradrenaline-induced cyclic AMP accumulation and its action on learning and memory is discussed.

Animals↗