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B Jarrott

Publications and source records attributed to B Jarrott.

At least 199 records · Page 11Linked to original sources
PubMed1972

Rapid axoplasmic transport of tyrosine hydroxylase in relation to other cytoplasmic constituents.

The transport of norepinephrine and two key enzymes involved in its synthesis, tyrosine hydroxylase (EC 1.14.3a) and dopamine beta-hydroxylase (EC 1.14.2.1), has been studied in relation to other axonal constituents in ligated chicken sciatic nerves. Norepinephrine, tyrosine hydroxylase, and dopamine beta-hydroxylase activity all increased proximal to the constriction over a 20-hr period. The rate of transport of norepinephrine, tyrosine hydroxylase, and dopamine beta-hydroxylase were calculated as 2.6, 1.9, and 3.4 mm/hr, respectively. The only enzyme marker to show a similar rate of accumulation was acetylcholinesterase (EC 3.1.1.7), a putative marker for endoplasmic reticulum. The rapid axoplasmic transport of tyrosine hydroxylase from the cell bodies to the terminals of sympathetic neurons may be adequate to account for the elevated amounts of this enzyme in chronically active axon terminals, without the necessity to invoke peripheral axonal synthesis of the enzyme to explain such elevated amounts.

Acetylcholinesterase↗
PubMed1971

Action of 6-hydroxydopamine on lamb sympathetic ganglia, vas deferens and adrenal medulla: a combined histochemical, ultrastructural and biochemical comparison with the effects of reserpine.

1. The effects of a single dose of 6-hydroxydopamine (6-OHDA) compared with those of chronic reserpine treatment were studied in lamb sympathetic neurones and adrenal medulla by a combination of fluorescence histochemistry, electron microscopy and radiochemical assay.2. In sympathetic ganglia, 6-OHDA produced a rise in noradrenaline concentration within 24 h, and falls in tyrosine hydroxylase and monoamine oxidase activities, whereas reserpine caused a fall in noradrenaline, a rise in tyrosine hydroxylase activity and no change in monoamine oxidase activity. The fluorescence of intra- and postganglionic axons increased greatly within 24 h of 6-OHDA, and there was a corresponding accumulation of large dense-core vesicles within many axons whose neurotubules were disrupted. The changes were almost reversed after 3 weeks.3. In the vas deferens, the concentration of noradrenaline and tyrosine hydroxylase and monoamine oxidase activities had all fallen 24 h after 6-OHDA treatment and had started to recover 3 weeks later. In the adrenal medulla, 6-OHDA did not alter NA concentrations but increased tyrosine hydroxylase activity whereas reserpine depleted noradrenaline and increased tyrosine hydroxylase activity.4. The changes produced in sympathetic ganglia by 6-OHDA may be due both to a direct action on the axoplasmic transport of noradrenaline containing vesicles and indirectly to the reaction of the neurones to loss of the integrity of their axons.

Adrenal Medulla↗
PubMed1971

Differences in the uptake, storage and metabolism of (+)- and (-)-noradrenaline.

1. The rate of uptake of (+)- and (-)-noradrenaline was measured in isolated perfused hearts of reserpine treated rats, mice and guinea-pigs by fluorimetric analysis of the removal of catecholamine from the perfusion medium. In rat and mouse heart (-)-noradrenaline was taken up significantly more rapidly than (+)-noradrenaline, but no stereochemical specificity was found for noradrenaline uptake in guinea-pig hearts.2. Using radioactively labelled (+)-(14)C-noradrenaline and (-)-(3)H-noradrenaline, the kinetic constants for uptake into noradrenaline-containing and dopamine-containing synaptosomes from rat brain were determined. The uptake by noradrenaline terminals in the hypothalamus had a higher affinity for (-)-noradrenaline than for the (+)-isomer, but no differences in affinity were found for uptake into dopamine terminals.3. When equal amounts of labelled (+)- and (-)-noradrenaline were injected in vivo in double isotope experiments, the (+)-isomer disappeared more rapidly than the (-)-isomer from rat heart and spleen, but no significant differences were found between the rates of disappearance of the two isomers from rat brain or in the whole mouse.4. Analysis of the radioactive metabolites of the two isomers of noradrenaline after administration of mixed doses of the labelled substances showed that a significantly higher proportion of (+)-noradrenaline was metabolized to normetanephrine than of (-)-noradrenaline, in the whole mouse, rat heart and rat brain.

Animals↗
PubMed1971

Changes in monoamine oxidase and catechol-0-methyl transferase activities after denervation of the nictitating membrane of the cat.

1. The question of cellular localizations of monoamine oxidase and catechol-o-methyl transferase, enzymes involved in the metabolism of noradrenaline, has been investigated by following the changes in the enzyme activity of the smooth muscle of the cat nictitating membrane after sympathetic denervation. Any falls in enzyme activity coinciding with the time course for degeneration of the sympathetic nerve endings (2-3 days) can reasonably be ascribed to a former localization of the enzyme within the sympathetic nerve.2. Monoamine oxidase activity of the inferior and medial smooth muscle was significantly reduced 3 days after sympathectomy and remained reduced 14 days after sympathectomy.3. A correlation was found between the fall in monoamine oxidase activity and the endogenous noradrenaline concentration of the contralateral normal muscle, indicating that the higher the endogenous noradrenaline concentration, the greater the fall in monoamine oxidase activity after denervation.4. It was concluded that the fall in monoamine oxidase activity after denervation indicated a former localization of the enzyme within the sympathetic nerve endings.5. The fall in monoamine oxidase activity of the denervated muscle was significantly less measured with benzylamine as a substrate than with tyramine. This suggested that the neuronal monoamine oxidase may have different properties than the extraneuronal enzyme.6. A small fall in the catechol-o-methyl transferase activity of denervated smooth muscle was found and a correlation between the fall in enzyme activity and endogenous noradrenaline indicated that in this smooth muscle a proportion of the catechol-o-methyl transferase activity may be of presynaptic origin.

Amines↗
PubMed1970

Uptake and metabolism of catecholamines in the perfused hearts of different species.

1. The uptake of (+/-)-(3)H-noradrenaline was studied in isolated perfused hearts of rat, mouse, guinea-pig, pigeon and toad (Bufo marinus), and the IC50 (concentration causing 50% inhibition) values for inhibition of uptake of (+/-)-(3)H-noradrenaline by (-)-noradrenaline were calculated. IC50 values ranging from 0.28 muM (rat heart) to 2.34 muM (toad heart) were found.2. In all species except the toad, (-)-noradrenaline showed a higher affinity than (-)-adrenaline for the uptake process, but the reverse was found for the toad heart.3. Mouse and pigeon hearts contained increasing amounts of metabolites of noradrenaline with increasing perfusion concentrations of noradrenaline, but the guinea-pig and toad hearts did not. The in vitro activities of noradrenaline catabolizing enzymes in heart homogenates were measured but did not explain the differences in the pattern of catabolism of noradrenaline found in the intact hearts of the different species.4. In all hearts except the toad, cocaine was an effective blocking agent for the uptake of (+/-)-(3)H-noradrenaline and led to an increase in (3)H-normetanephrine in these hearts. In the pigeon heart, cocaine plus phenoxybenzamine in the perfusate resulted in an inhibition of both (3)H-noradrenaline uptake and (3)H-normetanephrine formation.5. In guinea-pig and pigeon perfused hearts, the uptake of (3)H-noradrenaline into atria and ventricles reflected the relative concentrations of endogenous catecholamines in these regions, but this was not found for rat, mouse and toad hearts.6. It was concluded that species differences exist for both the accumulation and metabolism of catecholamines in isolated perfused hearts.

Animals↗
PubMedDate not supplied

Regional brain concentrations of neurotensin following amygdaloid kindled and cortical suprathreshold stimulation-induced seizures in the rat.

There is now considerable evidence that putative neuropeptides are involved in epileptogenic processes. Neurotensin (NT), which affects neuronal excitability in many parts of the CNS, is potentially relevant to the kindling phenomenon, but has not previously been studied in the kindling model of epilepsy. This study compared the short term (24 hr) and long term (3 wk) effects of amygdaloid kindled seizures, and the short term effects of non-kindled seizures (cortical suprathreshold stimulation-induced seizures, STS), on the concentrations of NT in 13 brain regions in the rat. Whereas kindled seizures produced neither short term nor long term changes in NT, the STS resulted in altered NT concentrations, with a decrease in the cortex and increases in the hippocampus and cervical spinal cord. These results reveal seizure-type specific changes in NT in 3 brain regions; and indicate that although NT does not appear to be involved in kindling, it may be important in the neurochemical mechanisms underlying STS.

Animals↗
PubMedDate not supplied

Electrophysiological and autoradiographical evidence for cholecystokinin A receptors on rat isolated nodose ganglia.

The sulphated octapeptide, cholecystokinin (CCK-8S), is believed to be a neurotransmitter of vagal sensory neurones, and here the presence of functional receptors for CCK-8S in the rat vagus nerve has been investigated by electrophysiological and autoradiographic techniques. CCK-8S caused concentration-dependent depolarizations when superfused over the rat isolated nodose ganglion at 37 degrees C as measured by a silicone grease gap technique. Concentration-response curves to CCK-8S were shifted to the right by low concentrations of the CCKA receptor antagonist, Devazepide, but not by the CCKB receptor antagonist, L-365,260, data which indicate that receptors were of the CCKA subtype. Consistent with this notion, the CCKB agonist, unsulphated CCK-8, was without effect until high concentrations (> 1 microM) were used. A synthetic analogue of CCK-8S, D-Tyr25(Nle28,31)-CCK 25-33S, which has been reported to be more stable and peptidase-resistant than CCK-8S, was equipotent with CCK-8S in depolarizing the nodose ganglion. When D-Tyr25(Nle28,31)-CCK 25-33S was labelled with 125I, it bound to tissue sections of nodose ganglion. By light microscopic autoradiography, silver grains were found to be highly localized over cell bodies of vagal sensory neurones. An excess of CCK-8S inhibited binding as did Devazepide, but not L-365,260, confirming that binding sites were CCKA subtype receptors. These results indicate the existence of functional CCKA receptors in the nodose ganglion and strengthen the case for the involvement of vagal sensory neurones in gastric emptying and satiety.

Animals↗
PubMedDate not supplied

Pharmacological characterization of bradykinin B1 and B2 receptors in IMR-90 and INT-407 human cell lines using a microphysiometer.

1. In the present study, we used a microphysiometer to measure bradykinin-induced acidification responses in IMR-90, a human lung fibroblast cell line, and INT-407, a human colonic epithelial cell line. Furthermore, we investigated the effect of 24 h exposure of transforming growth factor (TGF)-alpha on the bradykinin response in INT-407 cells. 2. Bradykinin (0.1-100 nmol/L) was potent in producing acidification responses in IMR-90 cells (pEC50 8.79+/-0.13; Hill slope 0.96+/-0.04) and INT-407 cells (pEC50 8.90+/-0.04; Hill slope 1.00+/-0.07). These responses were competitively antagonized by the bradykinin B2 receptor antagonist icatibant in both IMR-90 cells (apparent pKB = 8.54+/-0.15; Hill slope = 1.09+/-0.13 and 1.66+/-0.26 in the absence and presence of 10 nmol/L icatibant, respectively) and INT-407 cells (pKB = 8.12+/-0.07 (3, 10 and 30 nmol/L icatibant); Hill slope = 1.06+/-0.04). However, the bradykinin B1 receptor antagonist des-Arg9Leu8-bradykinin (3 micromol/L) had no effect on the bradykinin responses. 3. The non-peptide bradykinin B2 receptor antagonist FR173657 selectively antagonized bradykinin-induced acidification responses in INT-407 cells in a competitive manner (pKB = 8.76+/-0.10; Hill slope = 0.92+/-0.05) at lower concentrations (1 and 3 nmol/L) but in an insurmountable manner at higher concentrations (10 nmol/L; Hill slope = 1.04+/-0.09). This compound, at concentrations of 10 and 100 nmol/L (Hill slope = 1.38+/-0.15), also proved to be an insurmountable antagonist in IMR-90 cells. 4. The bradykinin B1 receptor selective agonist Lys0des-Arg10-bradykinin (0.1 nmol/L to 0.1 micromol/L) failed to produce acidification responses in IMR-90 cells, even after 24 h pre-incubation with bacterial lipopolysaccharide (0.1 microg/mL). 5. A 24 h pre-incubation of INT-407 cells with TGF-alpha (1, 10 and 100 ng/mL) caused a significant concentration-dependent decrease in maximal bradykinin response without affecting the pEC50. 6. In addition to this study being the first to use a microphysiometer to characterize bradykinin B2 receptors in cultured IMR-90 human lung fibroblast cells and INT-407 human colonic epithelial cells, we also showed that pre-incubation of INT-407 cells with TGF-alpha caused a significant decrease in maximal acidification response mediated by bradykinin B2 receptors.

Bradykinin Receptor Antagonists↗