Accumulation Of 3H-norepinephrine Research Articles

Contractions of canine vascular smooth muscle cells caused by ouabain are due to release of norepinephrine from adrenergic nerve endings.

Experiments were performed to determine whether the contractions of isolated canine blood vessels caused by ouabain are due solely to the release of endogenous norepinephrine. The response of segments of splenic arteries and veins and strips of splenic capsules to ouabain were compared before and after surgical sympathectomy. Successful denervation was demonstrated by absence of a contractile response to electrical stimulation, supersensitivity to exogenous norepinephrine, an extremely low content of endogenous norepinephrine, reduced accumulation of 3H-norepinephrine, and inability of electrical stimulation and tyramine to augment the overflow of 3H-norepinephrine. Ouabain augmented the overflow of 3H-norepinephrine from control but not from denervated splenic capsule. It caused contraction of control but not of denervated splenic arteries, veins, and capsules. Studies were also conducted in the same tissues and in segments of mesenteric and femoral arteries and of circular and longitudinal segments of the portal mesenteric vein before and after chemical sympathectomy with 6-hydroxydopamine. In these tissues, the contractile responses to electrical stimulation but not exogenous norepinephrine and prostaglandin F2 alpha were abolished. In the control tissues, ouabain caused strong contractions, whereas, in the denervated tissues, only a weak or no response to the glycoside occurred. The study demonstrates that, in isolated canine blood vessels, ouabain causes contraction of smooth muscle cells by virtue of its ability to release norepinephrine from the sympathetic nerves.

Effects of anisomycin and CNS stimulants on brain catecholamine synthesis

Mice were injected with anisomycin, an inhibitor of cerebral protein synthesis; d-amphetamine, strychnine, or caffeine was administered 30 min later. Fifteen min before sacrifice at 1 or 2 hr after injection of anisomycin, 3H-tyrosine was injected intravenously, and catecholamine synthesis rates were estimated by measurement of the specific activity of 3H-tyrosine and the accumulation of 3H-norepinephrine and 3H-dopamine. Anisomycin decreased synthesis rates of catecholamines, but this effect was not significantly affected by any of the CNS stimulants. These results suggest that the recently reported reversal of anisomycin-induced amnesia by these stimulants is not due to an attenuation of brain catecholamine synthesis inhibition.

Effects of cycloheximide, diethyldithiocarbamate and d-amphetamine on protein and catecholamine biosynthesis in mouse brain

C57 BL/6J mice were injected with cycloheximide, diethyldithiocarbamate, d-amphetamine, cycloheximide + D-amphetamine, or diethyldithiocarbamate + d-amphetamine and then given 3H-tyrosine 30 min before sacrificing at 0.5, 1.0, 1.5, 3.5, or 6.5 hr after the first drug injection. The brains were removed and analyzed for endogenous tyrosine, norepinephrine and dopamine; accumulation of 3H-norepinephrine and 3H-dopamine; 3H-tyrosine incorporation into protein and tyrosine specific activity. Cycloheximide alone had little effect on endogenous norepinephrine and dopamine, but markedly reduced the accumulation of 3H-norepinephrine and 3H-dopamine, and the incorporation of 3H-tyrosine into protein. d-Amphetamine reduced the effect of cycloheximide on the accumulation of newly synthesized catecholamines but had no effect on the inhibition of protein synthesis. Diethyldi-thiocarbamate markedly reduced endogenous norepinephrine and the accumulation of 3H-norepinephrine but had a negligible effect on protein synthesis. D-Amphetamine potentiated the effect of diethyldithiocarbamate on norepinephrine accumulation. These results are discussed in relation to the effects of the above drugs on memory.

Ethanol withdrawal in the rat: Involvement of noradrenergic neurons

Ethanol dependence was induced in rats by maintaining them for 3 weeks on a liquid diet containing ethanol. When ethanol was abruptly replaced with sucrose in the diet, animals showed withdrawal symptoms. Eight hours later, the accumulation in brain and heart of 3H-norepinephrine synthesized from 3H-tyrosine, and of 3H-norepinephrine metabolites was greater than in animals not undergoing withdrawal. An injection of ethanol (3 g/kg) 1 1 2 or 5 hours after the initiation of withdrawal resulted in less accumulation of newly synthesized 3H-norepinephrine and of 3H-norepinephrine metabolites in both brain and heart. If the rate of ethanol withdrawal was slow, i.e., the ethanol in the diet was replaced gradually with sucrose over a 3-day period, less accumulation of 3H-norepinephrine and 3H-norepinephrine metabolites occured in heart and brain than as a result of abrupt withdrawal. Also, no behavioral symptoms of withdrawal were observed. These results indicate that (a) gross withdrawal symptoms and the accompanying activation of noradrenergic neurons can be blocked during withdrawal by an acute dose of ethanol, and (b) ethanol withdrawal can be modified by altering the rate of withdrawal, a finding that may prove useful in clinical situations. We conclude that the withdrawal symptoms and the activation of noradrenergic neurons during withdrawal are caused by the sudden lack of ethanol in the system.

Dissociation of amphetamine-induced release of norepinephrine from inhibition of neuronal uptake in isolated brain tissue

Publisher Summary This chapter reviews the dissociation of amphetamine-induced release of norepinephrine (NE) from inhibition of neuronal uptake in isolated brain tissue. Neuronal uptake of 3H-norepinephrine into chopped rat brain tissue was measured by a method involving a 10 min incubation of chopped rat brain tissue with 10−7 M 3H-norepinephrine, and measuring total radioactivity in the incubation medium, and tissue. Drugs were added to the incubation medium 10 min before, and during the incubation with 3H-norepinephrine. Experimental samples were incubated at 37°C, and compared to control samples incubated at 0°C. It is found that because there is relatively little metabolism of 3H-norepinephrine in this 10 min exposure, 3H-norepinephrine was not separated from the deaminated metabolites. Results were expressed as tissue to medium ratios. This ratio approaches 1.0 at 0°C which indicates a lack of specific uptake at this temperature. The ratio was 7.1 ± 0.4 at 37°C in the absence of drugs, and this reflects approximately a sevenfold increase in uptake, and accumulation of 3H-norepinephrine into the tissue.

Effect of nerve stimulation and angiotensin on the accumulation of 3H-norepinephrine and the endogenous norepinephrine level in guinea pig vas deferens

The effect of angiotensin on the endogenous norepinephrine (NE) content and on the accumulation of 3H-NE was studied in the isolated guinea pig vas deferens stimulated at both the pre- and postganglionic level (hypogastric nerve and transmural stimulation). It was found that angiotensin blocked 3H-NE accumulation (uptake and retention and produced a depletion of endogenous NE in the unstimulated vas deferens. Continuous pre- and postganglionic stimulation at low-frequency (6/sec) did not produce any significant changes in the endogenous NE level, while high-frequency (50/sec) stimulation reduced it by 30–40 per cent. The accumulation of 3H-NE was impaired by continuous pre- and postganglionic stimulation and was dependent on the frequency of stimulation. With a high-frequency (50/sec), the accumulation was only 5–6 per cent of the control, suggesting that depolarization of the neuronal membrane, produced by nerve stimulation, blocks the re-uptake of NE and favors its release. It appears, therefore, that these two phenomena are sequential for a certain area of the neuronal membrane. Angiotensin abolished the inhibiting effect of nerve stimulation on 3H-NE uptake and retention. It is concluded that the effect of angiotensin on the endogenous NE level and on the accumulation of 3H-NE depends on the degree of impulse activity in the sympathetic nerve and the concentration of angiotensin used. The duality (or plurality) of the action of angiotensin in the stimulated and unstimulated guinea pig vas deferens suggests a possible modulating role of angiotensin in adrenergic neurotransmission.

Catecholamine metabolism in experimental hypertension in the rat.

The role of catecholamines was investigated in uninephrectomized Sprague-Dawley male rats made hypertensive by administration of desoxycorticosterone and a high salt diet. The accumulation of tritiated norepinephrine and the endogenous norepinephrine levels were measured in the various organs. The content of endogenous norepinephrine and the accumulation of 3 H-norepinephrine 1 hour after its injection were reduced in the heart, spleen, intestine, skeletal muscle, and kidney of hypertensive rats as compared to controls. Simultaneously, an increase in total 3 H-metabolites was also found in the hypertensive animals. A highly significant inverse relation was established between the level of blood pressure and the accumulation of 3 H-norepinephrine or endogenous norepinephrine levels in the heart. The abnormalities observed in the disposition of exogenously administered and endogenous norepinephrine do not appear to be secondary to a change in the distribution of cardiac output to the various organs. Since the initial uptake was normal in the hypertensive rats, the reduced capacity to accumulate norepinephrine seems to be related to a defect in the storage of norepinephrine.

Nervous Control of the Blood Vessels

Nervous Control of the Blood Vessels