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Subcellular localization of neutral red staining in Limulus ventral photoreceptors.

Limulus ventral photoreceptors are vitally stained by neutral red. In other systems such staining has been correlated with the presence of monoamines or neuropeptides. The stained cellular components in ventral photoreceptors are clusters of small ovoids which have been identified as residual bodies. These structures are unlikely candidates for monoamine or neuropeptide synthesis or storage sites, but may be part of the cyclic synthesis and degradation of photosensitive membrane. While vital staining with neutral red is a particularly useful method for identifying certain classes of neurons in vivo, in the case of ventral photoreceptors, the association of the vital staining property with the presence of a particular class of neurotransmitter candidates has proven difficult. Neutral red is useful, however, for visualizing the segmentation of ventral photoreceptors in vivo.

Animals↗

Mechanism-based inactivation of dopamine beta-monooxygenase in adrenal chromaffin cells.

Dopamine beta-monoxygenase (DBM, E.C. 1.14.17.1) is an attractive target point for possible modulation of adrenergic activity, and a variety of DBM-targeted pseudosubstrates and inhibitors have been developed in this laboratory and other laboratories. We now demonstrate the efficacy of a DBM-targeted mechanism-based inactivator, as well as enzymatic processing of two alternate DBM substrates, within functional adrenal chromaffin cells. When cultured adrenal medullary chromaffin cells were incubated with the mechanism-based inactivator 1-(4'-hydroxyphenyl)-1-(aminomethyl)-ethene (HOPAME), vesicular DBM activity was markedly decreased. Similarly, the alternate substrates 4'-hydroxyphenyl-2-aminoethyl sulfide and 4'-hydroxyphenyl-2-aminopropyl selenide each undergo uptake and DBM-catalyzed oxygenation within these cells. The simultaneous action of both the mechanism-based inactivator and an alternate substrate within functional chromaffin cells was also demonstrated. These results provide support for a direct mechanistic link between the enzymological properties of DBM-targeted adrenergic agents and their in-vivo pharmacological activities.

Adrenal Medulla↗

[Blood-pressure regulating drugs and intraocular pressure in animal experiments (author's transl)].

Electromanometric measurements of blood pressure and intraocular pressure, carried out in rabbits after the intravenous administration of Norphen, Peripherin, Sympatol, Hydergin, Tropodil, Complamin, Euphyllin and Vasculat showed that the changes in the pressure curves were largely in the same sense. Apart from a "passive" correlation of the intraocular pressure with the blood pressure, the local effects of pharmaceuticals administered are also discussed. The results obtained provide both general medicine and ophthalmology with insights into the mode of action of drugs, some of which are frequently administered. In addition, they serve both to provide information on the desirable curative effects of the drugs and to help prevent damage being done to the organ of sight.

Aminophylline↗

Competition of some biogenic amines for uptake into synaptic vesicles of the striatum.

Synaptic vesicles were isolated from the caudate nucleus of the pigs by differential centrifugation and incubated with labelled monoamines in the absence or in the presence of ATP-Mg(2+). Addition of ATP-Mg(2+) enhanced the uptake of (14)C-dopamine into the vesicles. Serotonin competitively inhibited the ATP-Mg(2+)-dependent uptake of (14)C-dopamine without influencing the uptake which took place in the absence of ATP-Mg(2+). Likewise, dopamine caused a dose-dependent inhibition of the ATP-Mg(2+)-dependent uptake of (14)C-serotonin without inhibiting the uptake in the absence of ATP-Mg(2+). Incubation of the vesicles with equal concentrations of(3)-dopamine and (14)C-serotonin revealed that the presence of the one amine competitively inhibited the ATP-Mg(2+)-dependent uptake of the other. Tyranimine competitively inhibited the ATP-Mg(2+)-dependent uptake of (14)C-dine, (14)C-serotonin and (14)C-noradrenaline into the vesicles; the uptake of the amines which took place in the absence of ATP-Mg(2+) was not impairedby tyramine. Analysis of the amine uptake by the ABC test showed that a mutual inhibition exists between dopamine and serotonin for the uptake into the synaptic vesicles. GABA did not influence the uptake of (14)C-dopamine either in the absence, or in the presence of ATP-Mg(2+)...

Adenosine Triphosphate↗

Norfenefrine: haemodynamic effects in healthy volunteers at rest and during orthostasis.

The haemodynamic effects of the alpha-mimetic norfenefrine 1.5-4.5 micrograms/kg/min i.v. were studied by invasive methods in six healthy male volunteers at rest and during orthostasis (90 degrees on tilt table). Norfenefrine was more effective at rest and during exercise in raising blood pressure in the pulmonary than in the systemic arterial system. It was concluded that norfenefrine should be effective in the treatment of patients with orthostatic dysregulation due to reduced venous tone.

2-Hydroxyphenethylamine↗

Catecholamine-induced cardiac hypertrophy: significance of proto-oncogene expression.

The effect of beta- and alpha-adrenergic stimulation on cardiovascular function and development of cardiac hypertrophy was studied in rats by measuring the heart weight/body weight and cardiac RNA/DNA ratios. Beta-receptor stimulation with isoproterenol over 3 days induced an increase in the biosynthesis of cardiac adenine nucleotides, myocardial protein synthesis, and the heart weight/body weight ratio. The isoproterenol-induced metabolic effects were prevented by simultaneous beta-adrenergic blockade with propranolol. Alpha-adrenergic stimulation with norfenephrine for 3 days induced an increase in heart rate, total peripheral resistance, the myocardial RNA/DNA, and left ventricular weight/body weight ratio. The calcium antagonist verapamil prevented the hemodynamic changes but did not influence the development of cardiac hypertrophy. The alpha-adrenergic blocker prazosin reversed the norfenephrine-induced functional changes and prevented cardiac hypertrophy. Norepinephrine was infused into isolated perfused working rat hearts to elucidate some molecular biological changes that precede the development of cardiac hypertrophy. It increased transiently and sequentially the mRNA of c-fos and c-myc. This enhancement occurred at about the same time as that induced by elevation of pre- and afterload but was more pronounced. These findings were compared with those obtained in other studies assessing the effects of catecholamines on proto-oncogene expression. Combination of norepinephrine with pre- and afterload elevation induced the c-fos mRNA signal to appear earlier, to be more pronounced, and to persist for a longer period of time. Similar results were obtained in regard to the c-myc mRNA. These findings indicate that the combination of two hypertrophy-inducing stimuli which may cause a higher degree of cardiac hypertrophy in vivo induce an earlier, more pronounced, and longer lasting expression of the proto-oncogenes c-fos and c-myc.

Adrenergic alpha-Agonists↗

A multichannel native fluorescence detection system for capillary electrophoretic analysis of neurotransmitters in single neurons.

A laser-induced native fluorescence detection system optimized for analysis of indolamines and catecholamines by capillary electrophoresis is described. A hollow-cathode metal vapor laser emitting at 224 nm is used for fluorescence excitation, and the emitted fluorescence is spectrally distributed by a series of dichroic beam-splitters into three wavelength channels: 250-310 nm, 310-400 nm, and >400 nm. A separate photomultiplier tube is used for detection of the fluorescence in each of the three wavelength ranges. The instrument provides more information than a single-channel system, without the complexity associated with a spectrograph/charge-coupled device-based detector. With this instrument, analytes can be separated and identified not only on the basis of their electrophoretic migration time but also on the basis of their multichannel signature, which consists of the ratios of relative fluorescence intensities detected in each wavelength channel. The 224-nm excitation channel resulted in a detection limit of 40 nmol L-1 for dopamine. The utility of this instrument for single-cell analysis was demonstrated by the detection and identification of the neurotransmitters in serotonergic LPeD1 and dopaminergic RPeD1 neurons, isolated from the central nervous system of the well-established neurobiological model Lymnaea stagnalis. Not only can this system detect neurotransmitters in these individual neurons with S/N>50, but analyte identity is confirmed on the basis of spectral characteristics.

Animals↗

[Problems in carrying out baroreflex sensitivity measurements in clinical routine practice: practicability and complications].

Measurement of baroreflex sensitivity is a new method to identify patients after myocardial infarction with a high risk for sudden cardiac death, ventricular tachycardia or ventricular fibrillation. In this retrospective study the baroreflex sensitivity was obtained noninvasively by measuring the systolic blood pressure blood pressure with a FINAPRES-device and correlating this with the R-R intervals of the ECG after raising blood pressure with an intravenous dose of Norfenefrin-hydrochloride (Novadral). According to other investigators a correlation of > 0.7 with a significance of p < 0.05 was recommended for evaluable results with a baroreflex sensitivity < 3 ms/mm Hg being judged as decreased. We investigated 302 patients (mean age 59 +/- 17 years, 224 males, 78 females). 75% of the investigations showed acceptable results. In 77 cases (25%) reasonable results could not be achieved. We found premature ventricular beats to be responsible in 18 investigations (6% of all investigations). 41 (13.1%) of all investigations were not evaluable because of bad correlation for unknown reason. When we looked closely at these nonevaluable results, we found a significantly higher number of patients with impaired left ventricular ejection fraction (< 40%), diabetes or inducible sustained ventricular tachyarrhythmia in the electrophysiologic study in this group. During all investigations no severe side effects were observed. We conclude that the noninvasive measuring of the baroreflex sensitivity is a save method and leads to reasonable results in 75% of the investigations. In 13.1% it is not possible for unknown reason to achieve sufficiently correlating values. These measurements cannot be evaluated from nowadays' standards and have to be further investigated as they may indicate a population at high risk.

Adult↗

[Chemoreflex and baroreflex sensitivity in patients with survived sudden cardiac death].

INTRODUCTION: To evaluate patients with an increased risk of sudden cardiac death the analysis of ventricular late potentials, heart rate variability and baroreflexsensitivity is helpful. However, the prediction of malignant arrhythmic events cannot be performed with sufficient accuracy. For a better identification of high risk patients other methods are necessary. In this study the impact of the chemoreflexsensitivity for the prediction of ventricular tachyarrhythmias was investigated. METHODS: Out of 44 patients included in the study, 23 were survivors of sudden cardiac death (SCD). Seven patients suffered from sustained monomorphic ventricular tachycardias, 14 had no arrhythmic events in their prior history. For the investigation of the baroreflexsensitivity (BRS) systolic blood pressure was augmented by Norfenefrin (Novadral) and the resulting increase of RR-intervals was measured in the surface-ECG. For determination of the chemoreflexsensitivity (ChRS) the ratio of the RR-interval-shift and the blood pressure shift during a 5-min inhalation of oxygen with a nose mask was formed. RESULTS: Patients with aborted SCD showed significantly decreased values for the ChRS compared to those patients without an arrhythmic event in their prior history (2.49 +/- 1.86 vs. 6.75 +/- 6.79 mm Hg, p < 0.001). In contrast, for the BRS no significant differences could be found (5.23 +/- 3.95 vs. 5.34 +/- 3.10 mm Hg, p = n.s.). Patients with aborted sudden cardiac death and inducible tachyarrhythmias during the electrophysiologic study showed significantly lower values of BRS and ChRS compared to patients without inducibility. CONCLUSION: As a new method for identification of patients with an increased risk of sudden cardiac death the analysis of chemoreflexsensitivity seems feasible and indicates an increased arrhythmic risk with a high sensitivity. The predictive impact has to be corroborated in larger patient collectives by prospect studies.

Autonomic Nervous System↗