SEARCH · PubMed Health

Results for “Norepinephrine”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 919 records · Page 51Linked to original sources

PubMed1988

Circadian rhythms and influence of light on serotonin, norepinephrine, and epinephrine contents in the pineal-paraphyseal complex of soft-shelled turtles (Lissemys punctata punctata).

The aims of the current investigation were to examine the circadian rhythms in the pineal-paraphyseal amines and indoleamine in juvenile turtles. An attempt was also made to study the influence of photoperiod on pineal activities in adult turtles. Serotonin, norepinephrine, and epinephrine levels were studied at four different time intervals (0600, 1200, 1800, and 2400 hr) of a 24-hr period. Increased serotonin level was observed during day and trough values during night, but the norepinephrine and epinephrine levels showed reverse changes. Continuous light (24L:0D) or long photoperiod (22L:2D) resulted in an elevation of serotonin level and diminution of norepinephrine level, but continuous darkness (0L:24D) or short photoperiod (2L:22D) showed reverse changes. Epinephrine level altered in parallel to that of norepinephrine with long (22L:2D) or short (2L:22D) photoperiod, but remained unaltered with continuous light (24L:0D) or continuous darkness (0L:24D). It is suggested that circadian rhythms exist in pineal-paraphyseal amines and indoleamine in juvenile turtles like that of adult turtles. It is also suggested that light greatly modulates serotonin, norepinephrine, and epinephrine contents in the pineal-paraphyseal complex of the soft-shelled turtle.

Animals↗

PubMed1989

Decrease with senescence in the norepinephrine-induced phosphorylation of myofilament proteins in isolated rat cardiac myocytes.

(1) The effects of norepinephrine on protein phosphorylation in isolated rat cardiac ventricular myocytes were determined by autoradiography on 32P-labelled proteins separated by electrophoresis; (2) In cells from young adult rats (6 months old) there was a marked increase due to norepinephrine (10(-8) to 10(-4) M) in the incorporation of 32P into proteins identified on the grounds of molecular weight as troponin I and C-protein: in cells from senescent rats (24 months old) this increase was much attenuated. (3) Age-associated decrements in protein phosphorylation were much diminished when maximally effective concentrations of the adenylate cyclase-activator forskolin and the cyclic AMP analog 8(4-chlorophenylthio) cyclic AMP were used instead of norepinephrine. Moreover, age-associated differences were abolished if the phosphodiesterase inhibitor isobutylmethylxanthine was present in addition to norepinephrine, or alone. (4) Study of the rates of dephosphorylation of troponin I, as initiated with the beta-adrenergic antagonist propranolol, showed no change in half-time as a function of age: this indicates no change in protein phosphatase activity. (5) These results suggest that there is less active net formation of cyclic-AMP in senescent heart cells in response to the neurotransmitter norepinephrine, giving a lesser activation of c-AMP-dependent protein kinase and less phosphorylation of these target proteins.

Actin Cytoskeleton↗

PubMed1984

Alpha-2 adrenergic regulation of norepinephrine release in the rat submandibular gland as measured by HPLC-EC.

In many tissues, norepinephrine appears to inhibit its own release through an interaction at alpha adrenergic receptors. We have developed an assay for measuring the release of endogenous norepinephrine based on HPLC and have studied the regulation of release in the rat submandibular gland by alpha adrenergic antagonists. The method uses electrochemical detection to quantitate norepinephrine released from tissue slices and does not require preloading of the tissue with [3H]norepinephrine. Yohimbine, an alpha-2 adrenergic antagonist, potentiates by 50% the release caused by potassium induced depolarization with an EC50 of 0.14 microM. Prazosin, an alpha-1 antagonist, has a similar effect, but is less potent with an EC50 of 0.77 microM. Thus, the alpha adrenergic receptor mediating the regulation of norepinephrine release is of the alpha-2 subtype. The observed equal efficacies and lack of additivity of release potentiation by yohimbine and prazosin at maximal doses suggest that both drugs act at the same receptor. The five-fold difference in potency between prazosin and yohimbine is consistent with the recent observations indicating species differences between rodent and non-rodent alpha-2 adrenergic receptors.

Adrenergic alpha-Antagonists↗

PubMed1985

Mass spectrometric measurements of norepinephrine synthesis in man from infusion of stable isotope-labelled L-threo-3,4-dihydroxyphenylserine.

The kinetics of stable isotope-labelled L-threo-3, 4-dihydroxyphenylserine(L-threo-DOPS), an immediate precursor of (-)-norepinephrine, was studied to investigate the pharmacologic mechanism of its therapeutic effect on orthostatic hypotension in familial amyloid polyneuropathy(FAP) and on akinesia and freezing in parkinsonism. [13C,D]-L-threo-DOPS was synthesized, and 100 mg of the compound was infused for 2 h into two normal subjects, two FAP patients and two patients with the degenerative diseases of the central nervous system. Labelled and endogenous norepinephrine in urine and plasma was assayed simultaneously by gas chromatography/mass spectrometry. The results indicate that the increase in norepinephrine in biological fluids after administration of L-threo-DOPS is attributable mostly to norepinephrine derived from L-threo-DOPS, not to pre-formed endogenous norepinephrine released by L-threo-DOPS.

Atrophy↗

PubMed1990

Cocaine inhibition of ligand binding at dopamine, norepinephrine and serotonin transporters: a structure-activity study.

Structure-activity relationships for cocaine and analog binding at the dopamine, norepinephrine and serotonin transporters were determined. Cocaine inhibition of ligand binding to each of these sites has a stereospecific requirement for the levorotatory isomer. Binding potencies of cocaine derivatives involving N-substitution, C2 and C3 substituent modifications, however, revealed differences in structure-activity relationships for cocaine binding at the transporters. Removal of the N-methyl groups produced little change in binding potency at the dopamine transporter site but produced increases in binding potency at norepinephrine and serotonin transporter sites. Changes in structure at the C2 substituent produced changes in binding potency at the dopamine transporter which were generally similar in direction, but not necessarily in magnitude at the norepinephrine and serotonin transporters. Modifications to the C3 substituent, especially substitution of a hydroxyl moiety, produce changes in affinity at norepinephrine and serotonin transporters which are much larger than those observed at dopamine transporters. In general, our results indicate that unique structural requirements exist for each transporter site, but that cocaine binding at norepinephrine and dopamine transporters can be described by more similar structure-activity relationships than those found for the serotonin transporter. Requirements for cocaine binding to the dopamine transporter, which we have previously shown to be associated with the reinforcing effects of cocaine, include levorotatory stereospecificity, the benzene ring at C3, at least some portions of the tropane ring, and the presence of the C2 methyl ester group in the beta conformation.

Animals↗

PubMed1992

Chromogranin A correlates with norepinephrine release rate.

Chromogranin A (CgA) is an acidic protein co-released with catecholamines during exocytosis from sympathetic nerve terminals and chromaffin cells. Previous work has demonstrated that large scale perturbations in sympathetic nervous system (SNS) functioning result in corresponding changes in CgA levels in plasma. Little is known about the physiologic significance of CgA. We hypothesized that, since CgA and catecholamines are co-released from the same storage vesicles, and since CgA is not subject to reuptake or enzymatic metabolism, plasma CgA should reflect norepinephrine release from sympathetic terminals. We therefore measured venous CgA, norepinephrine levels, and norepinephrine release rate in 30 unmedicated subjects. Although the correlation of CgA with plasma norepinephrine was only modest (r = 0.37, p less than 0.05), its correlation with norepinephrine release rate was highly significant (r = 0.58, p less than 0.001). Thus, CgA may offer a novel perspective on peripheral sympathetic activity.

Adult↗

PubMed1992

Chronic cocaine administration decreases norepinephrine-induced phosphoinositide hydrolysis in rat aorta.

The effect of chronic cocaine administration on norepinephrine stimulated hydrolysis of inositol 1,4,5-trisphosphate from the membrane phosphatidylinositol phosphate pool in isolated rat aorta was investigated. Rats received saline (controls), or 10 or 20 mg/kg cocaine once a day for 15 days. This treatment resulted in a dose-dependent reduction in norepinephrine (0.36 microM) stimulated phosphoinositide hydrolysis. The effect of acute cocaine was determined by adding 30 microM cocaine to the in vitro incubation solution. When aortas were exposed to cocaine and norepinephrine simultaneously, in vitro, inositol phosphate formation doubled. By itself, cocaine did not affect phosphoinositide hydrolysis. Contraction of aortic helical strips by norepinephrine decreased in tissues from rats chronically treated with 20 mg/kg cocaine. In vitro cocaine shifted the norepinephrine concentration/response curve to the left and increased the maximum response. Neither acute nor chronic cocaine treatment affected prazosin's apparent dissociation constant, suggesting that cocaine did not affect receptor affinity. These data suggest that chronic, but not acute cocaine administration may interfere with pharmacomechanical coupling in rat aorta.

Animals↗

PubMed1985

Blunted norepinephrine responsiveness to changing energy states in obese subjects.

We have previously reported in lean subjects a significant relationship between plasma norepinephrine metabolism and energy state. The present study has examined in six obese men the response in plasma norepinephrine flux to ten day periods of overeating (+ 1000 kcal/m2 above isocaloric requirements) or undereating (400 kcal/d). Despite significant gains or losses in body weight, norepinephrine flux, measured during constant infusions of 3H-l-norepinephrine, failed to change significantly. Measurements of glucose utilization during constant infusions of insulin, showed significant changes with changing energy state, falling with overeating and rising with undereating. Insulin sensitivity was not correlated with plasma norepinephrine metabolism.

Adolescent↗

PubMed1980

Effects of prostaglandins E2, I2 and F2 alpha, arachidonic acid and indomethacin on pressor responses to norepinephrine in conscious rats.

The effects of prostaglandins E2 (PGE2), I2 (PGI2) and F2 alpha (PGF2 alpha), arachidonic acid and indomethacin on pressor responses to norepinephrine were examined in conscious rats. Intravenously infused PGE2, (0.3, 1.25 micrograms/kg/min), PGI2 (50, 100 ng/kg/min), PGF2 alpha (1.8, 5.4 micrograms/kg/min) and arachidonic acid (0.7, 1.4 mg/kg/min) did not change the basal blood pressure. Both PGE2 and PGI2 significantly attenuated pressor responses to norepinephrine, whereas PGF2 alpha significantly potentiated them. Arachidonic acid, a precursor of the prostaglandings (PGs), significantly attenuated pressor responses to norepinephrine. Since the attenuating effect of arachidonic acid was completely abolished by the pretreatment with indomethacin (5 mg/kg), arachidonic acid is thought to exert an effect through its conversion to PGs. On the contrary, intravenously injected indomethacin (0.2--5.0 mg/kg) facilitated pressor responses to norepinephrine in a dose-related manner without any direct effect on the basal blood pressure. These results suggest that endogenous PGs may participate in the regulation of blood pressure by modulating pressor responses to norepinephrine in conscious rats.

Animals↗

PubMed1982

Peptidergic regulation of norepinephrine induced feeding.

The inhibitory effect of a variety of substances on feeding induced by norepinephrine (20 micrograms ICV) was studied. Subcutaneous administration of opiate antagonist, naloxone, inhibited norepinephrine-induced eating at 10 and 5 mg/kg, but not a 1 mg/kg. Intraventricular administration of the GABA antagonist, bicuculline, produced a dose related decrease in food ingestion. The putative satiety hormones, bombesin (10 micrograms/kg; subcutaneously) and cholecystokinin octapeptide (10 micrograms/kg; subcutaneously) also reduced norepinephrine induced eating, as did ICV administration of calcitonin (2 units). Neither thyrotropin-releasing hormone (1 microgram ICV) nor its metabolits, histidyl-proline diketopiperazine (1 microgram ICV) altered norepinephrine-induced feeding. The studies reported here suggest a neuromodulatory role of peptides in the central regulation of norepinephrine-induced feeding.

Animals↗

PubMed1991

Influence of reduced presynaptic myocardial norepinephrine stores on left ventricular contractility.

Many investigators have reported that myocardial norepinephrine content is decreased in congestive heart failure. However there have been no studies of how decrease in myocardial norepinephrine might influence myocardial contraction. To clarify whether decreased myocardial norepinephrine per se affects myocardial contraction, we observed the change in left ventricular contractility during 30 min of left stellate ganglion stimulation in control and acutely reserpinized dogs. We obtained left ventricular max dp/dt and left ventricular end-systolic pressure-segment length relationships as indicators of left ventricular contractility. Both parameters decreased after left stellate ganglion stimulation in reserpinized dogs (left ventricular max dp/dt: 2064 +/- 200 to 1608 +/- 168 mmHg/s, left ventricular end-systolic pressure-segment length slope 117 +/- 22 to 79 +/- 14 mmHg/mm, n = 8, P less than 0.05), while they did not change in controls. In reserpinized dogs, left ventricular norepinephrine content decreased to one-third that of controls before the stimulation, and further decreased after stimulation. These data indicate that lowered myocardial norepinephrine itself may be responsible for the negative effect on left ventricular contractility in congestive heart failure.

Animals↗

PubMed1994

Localization of c-myc protooncogene expression in the rat heart in vivo and in the isolated, perfused heart following treatment with norepinephrine.

We have investigated the expression of the protooncogene c-myc in rat hearts following exposure to norepinephrine, both in vivo and in isolated perfused preparations. Both chronic and acute norepinephrine treatment produced a rapid, transient elevation of c-myc mRNA in adult rat hearts, but chronic infusion produced a second, larger increase. This expression profile was characteristic for c-myc since it was not found for four other protooncogenes. In the isolated, perfused heart, addition of norepinephrine to the perfusion buffer and elevation of perfusion pressure separately increase c-myc mRNA suggesting both direct hormonal and hemodynamic factors might be important in vivo. Immunocytochemistry showed that Myc protein accumulated predominantly in the nuclei of non-myocyte cells following norepinephrine treatment indicating that expression at the mRNA level culminated in protein synthesis. These findings suggest that the c-myc expression observed in the hypertrophying adult heart following exposure to norepinephrine may be associated with proliferating cells like fibroblasts rather than cardiomyocytes.

Animals↗

PubMed1995

Plasma norepinephrine, myocardial damage and left ventricular systolic function in Chagas' heart disease.

The functional status of the sympathetic nervous system in Chagas' heart disease is still the subject of intense controversy. To determine the nature of the abnormalities of the sympathetic nervous system, we measured the plasma norepinephrine concentration of chagasic patients with varying degrees of myocardial damage. Thirty-six patients with positive serology for Chagas' disease were studied. Twenty patients were in Functional Class I (New York Heart Association), 10 were in Functional Class II and six were in Functional Classes III-IV. Cardiac catheterization was performed in 24 patients. The asymptomatic patients had a plasma norepinephrine concentration (121 +/- 37 pg/ml, mean +/- S.D.) not different from normal controls (103 +/- 59 pg/ml). The symptomatic patients, however, had a significantly elevated plasma norepinephrine concentration (665 +/- 354 pg/ml, P < 0.001). The baseline heart rate of the asymptomatic and symptomatic patients directly correlated with the plasma norepinephrine concentration (r = 0.69, P < 0.0001). The symptomatic patients had larger ventricular volumes, higher left ventricular end-diastolic pressures and lower ejection fractions than the asymptomatic patients and normal controls. The plasma norepinephrine concentration correlated linearly with the left ventricular end-diastolic volume (r = 0.77, P < 0.0001), and non-linearly with the ejection fraction (r = -0.70, P < 0.0001) and the left ventricular end-diastolic pressure (r = 0.53, P < 0.007). These results indicate that, in Chagas' heart disease as in most other cardiac diseases, sympathetic nervous system activation is a late and compensatory phenomenon. In other words, sympathetic activation is very likely related to the progressive impairment of left ventricular function.

Adult↗

PubMed1993

Effect of 4-(4-methoxy-1,2,5-thiadiazol-3-yl)-1-methyl-1,2,3,6-tetrahydropyridine , an analog of MPTP, on mouse heart norepinephrine and brain catecholamines.

An analog of MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) with a thiadiazole substituent in place of the phenyl ring was compared to MPTP in mice for its ability to deplete striatal dopamine and its metabolites and norepinephrine in the frontal cortex and heart. One week after the last of 4 daily s.c. injections, MPTP at 20 mg/kg depleted mouse striatal dopamine, DOPAC and HVA as well as norepinephrine in the frontal cortex. One week after 4 daily s.c. doses of 4-(4-methoxy-1,2,5-thiadiazol-3-yl)-1-methyl-1,2,3,6-tetrahydro pyr idine (MZTP) at doses as high as 80 mg/kg, there was no effect on brain catecholamines. A single dose of MPTP (10 mg/kg s.c.) depleted heart norepinephrine concentration 24 h after injection. MZTP had no effect on heart norepinephrine at 10 mg/kg s.c., but did significantly deplete mouse heart norepinephrine 24 h after a dose of 20 mg/kg s.c.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

PubMedDate not supplied

Rat tail artery norepinephrine release: age and effect of mitochondrial blockade.

An age-related increase in stimulation-evoked fractional norepinephrine release has been demonstrated in tail artery of Fischer-344 rats from 6 to 20 months of age. Previous studies have ruled out alterations in function of uptake mechanisms, metabolism, or feedback via prejunctional alpha-2 adrenoceptors, suggesting that an age-related decline in calcium homeostasis may be responsible. To test this possibility, stimulation-evoked fractional norepinephrine release from perivascular adrenergic nerves of rat tail arteries in the presence of a blocker of mitochondrial calcium uptake, dinitrophenol (100 microM), was measured using HPLC with electrochemical detection. When the mitochondrial proton gradient was dissipated by dinitrophenol, tail arteries from 20-month-old animals showed a marked increase in stimulation-evoked norepinephrine release whereas arteries from 6-month-old animals were not affected. One hypothesis is that the inhibition of mitochondrial calcium uptake in the adrenergic nerves from older animals resulted in an elevated intracellular calcium level. In agreement with this idea, when extracellular calcium was raised from 1.6 to 5 mM, stimulation-evoked norepinephrine release was increased in the 6-month tail arteries in the presence of dinitrophenol. These data suggest that there may be a decline in calcium regulation in older nerves leading to increased norepinephrine release with advancing age.

Aging↗

PubMed1992

Endogenous opioid regulation of norepinephrine release in guinea pig hippocampus.

Release of endogenous norepinephrine was detected in guinea pig hippocampal slices using a radioligand displacement assay. Focal electrical stimulation released endogenous norepinephrine and caused a calcium-dependent reduction in specific [3H]propranolol binding at beta-adrenergic receptors in the brain slice. The mu-opioid agonist PL017 decreased norepinephrine release, and the inhibition by PL017 could be blocked by the opioid antagonist naloxone. Endogenous opioid peptides concomitantly released by tissue stimulation also decreased norepinephrine release in a naloxone-sensitive manner. These results support the hypothesis that endogenous opioids can regulate excitability in the hippocampus by presynaptic modulation of norepinephrine release.

Animals↗

PubMed1992

Norepinephrine-induced increase in sympathetic neuron-derived prostaglandins is independent of neuronal release mechanisms.

The contribution of exocytosis to norepinephrine-stimulated prostaglandin release from sympathetic postganglionic neurons was evaluated in homogenates of adult rat superior cervical ganglia. Incubation of ganglion homogenates with norepinephrine (1 mM) for 30 min caused an increased release of prostaglandin E2 and prostaglandin I2 (measured as the stable metabolite, 6-keto-PGF1a). Neither tetrodotoxin (10 mM), K+ (120 mM), nor EDTA in Ca(2+)-free buffer affected prostaglandin generation under basal and norepinephrine-stimulated conditions. These results suggest that the increase in prostaglandin production by sympathetic neurons after norepinephrine administration is not through the release of previously synthesized intracellular stores. Instead, the increase in prostaglandins in response to norepinephrine appears to be explained by de novo synthesis.

Animals↗

PubMed1975

[3H] norepinephrine binding by rat glial cells in culture. Lack of correlation between binding and adenylate cyclase activation.

Subcellular fractions prepared from rat glial cells in culture (clonal line c6) were used in an attempt to characterize the adrenergic receptor involved in adenylate cyclase activation. Both [3H] norepinephrine binding and enzyme activation were measured under identical experimental conditions. Binding sites for norepinephrine could be detected; their main characteristics were: apparant Km: 4 - 10-6 M, macimal capacity: 20 pmol/mg protein. Their stereospecificity towards structually related drugs was found to be different from the stereospecificity of the receptor involved in adenylate cyclase activation. Thus, 3-methoxydopamine (a competitive inhibitor of norepinephrine for adenylate cyclase activation), phenylephrine (a partial adrennergic agonist) and the blocking agent propranolol were unable to compete with [3H] norepinephrine for binding. On the other hand, several molecules like dopa bearing a catechol group and which are unable to interact with the adenylate cyclase as agonists or competitive inhibitors strongly inhibited [3H] norepinephrine binding. As in several other systems so far studied, the presence on the glial cell's membrane of a large number of "catechol-binding sites" makes it difficult to characterize the beta-adrenergic receptor.

Adenylyl Cyclases↗