Allan T. Hanretta

Is taurine a hypothalamic neurotransmitter? : a model of the differential uptake and compartmentalization of taurine by neuronal and glial cell particles from the rat hypothalamus

Although taurine has been postulated to be a neurotransmitter or neuromodulator in the mammalian CNS, little is known concerning its role in brain function. Evidence suggesting that taurine may influence endocrine and homeostatic mechanisms via the hypothalamus resulted in our investigations into its function in this brain region. The main objectives of the research were to characterize the specific binding, uptake, and release of taurine in the hypothalamus. A specific aim was to examine the proposed neurotransmitter role for taurine in the hypothalamus. This was accomplished by comparing the characteristics and properties of the binding, uptake, and release of taurine with those for the classical neurotransmitters which satisfy the criteria for a neurotransmitter. On such a comparative basis, the characteristics of taurine uptake satisfy the neurotransmitter criterion of inactivation of taurine in the hypothalamus. However, the observed characteristics of taurine binding and release in the hypothalamus do not satisfy the respective neurotransmitter criteria of specific receptors and Ca2+-dependent evoked release. Therefore, solely on the basis of the experimental observations reported herein, we must conclude that taurine apparently does not function as a neurotransmitter in the hypothalamus. Two uptake systems were found in the P2 fraction, a high affinity uptake system and a low affinity uptake system. Uptake systems for taurine have previously been reported in glial and nerve cell homogenates, and therefore, because of the known contamination of crude synaptosomal preparations with glial particles, we sought to determine the cellular origin of the two taurine uptake systems in our crude preparation. Using a variety of diverse biochemical techniques such as hypo-osmotic shock, release experiments and Arrhenius plots, we determined that physical changes of the media or depolarizing stimuli which would influence neuronal and glial cell particles differently, also had differing effects on high and low affinity taurine uptake or its release from the respective uptake compartments. We conclude that the high affinity taurine uptake system/compartment is located on/in neuronal membranes/particles/particles and that the low affinity taurine uptake system/compartment is located on/in neuronal membranes/particles and that model for the differential cellular transport and compartmentalization of taurine into neuronal and glial cells has important implications concerning its possible role in the CNS.

Properties of spontaneous and evoked release of taurine from hypothalamic crude P2 synaptosomal preparations

Recent studies suggest that taurine may function as a neurotransmitter in the hypothalamus. We examined this role for taurine by characterizing the high K+- and veratridine-evoked release, and the spontaneous release of [3H]taurine from superfused synaptosomal pellets (once-washed crude P2 fractions) prepared from rat hypothalami. Exposure of washed crude P2 synaptosomal pellets which had been preloaded with a concentration of [3H]taurine (1.5 microM) in the high affinity uptake range to either 56 mM K+ or 100 microM veratridine evoked a Ca2+-independent release of [3H]taurine. Exposure of washed crude P2 synaptosomal pellets, which had been preloaded with a concentration of [3H]taurine (2 mM) in the low affinity uptake range to 56 mM K+, induced a Ca2+-independent release of [3H]taurine, whereas 100 microM veratridine did not, either in the presence or absence of Ca2+. These observations support the hypothesis that the high affinity uptake system is located on neuronal membranes with evoked release occurring from a non-vesicular pool of taurine in the neuronal cytoplasm. In contrast, the low affinity uptake system appears to be located on glial membranes with evoked release occurring from a pool of taurine in the glial cytoplasm. Spontaneous [3H]taurine efflux from the high affinity uptake pool in the crude P2 synaptosomal pellet was not Ca2+-dependent. Furthermore, efflux was significantly reduced when NaCl was osmotically replaced with choline chloride in the superfusing medium. These observations suggest that the evoked release of taurine is not simply a reversal of the Na+-dependent high affinity taurine uptake carrier, but accomplished through some other unknown mechanism. The results presented in this report do not support a neurotransmitter role for taurine in the hypothalamus.

Combined use of ECT with duloxetine and olanzapine: a case report.

A 38-year-old woman with medication-resistant major depression and posttraumatic stress disorder was treated with electroconvulsive therapy (ECT) concurrent with a duloxetine-olanzapine combination. The treatment resulted in complete resolution of major depression without any complications. This case report suggests that treatment with the combination of duloxetine and olanzapine concurrently with ECT was found safe and uncomplicated. The literature on the combined use of antidepressants and ECT is briefly reviewed.

Possible Reduction in Posttraumatic Stress Disorder Symptoms with Oxcarbazepine in a Patient with Bipolar Disorder

OBJECTIVE To report the effect of oxcarbazepine in a patient with bipolar illness and posttraumatic stress disorder (PTSD). CASE SUMMARY A 38-year-old white woman with PTSD and bipolar disorder who had partially responded to carbamazepine was treated with oxcarbazepine. Within a month of initiation of treatment with oxcarbazepine, she reported progressive improvement in her PTSD symptoms. As oxcarbazepine monotherapy with 750 mg twice daily continued, she reported significant reduction of her PTSD symptoms and stabilization of her mood. She tolerated oxcarbazepine without adverse effects. DISCUSSION PTSD symptoms tend to wax and wane. Spontaneous remission also occurs in some patients with PTSD. There are a few reports indicating that carbamazepine alleviates PTSD symptoms. Since oxcarbazepine is an analog of carbamazepine, it is theorized that oxcarbazepine also has efficacy in significantly reducing PTSD symptoms. CONCLUSIONS There are case reports and uncontrolled studies suggesting that antiepileptic drugs (AEDs) alleviate PTSD symptoms. Oxcarbazepine may also benefit patients with PTSD. However, controlled studies are needed to investigate the use of AEDs in patients with PTSD and bipolar disorder.

The relationship between sodium and high-affinity taurine uptake in hypothalamic crude P2 synaptosomal preparations

Two uptake systems for taurine transport in a rat hypothalamic crude synaptosomal preparation were identified. The true transport constants were, for the high-affinity uptake system,Km=240 μM andV (maximum velocity)=400 nmol/g protein/min, and for the low-affinity uptake system.Km=5290 μM and V=1640 nmol/g protein/min. The initial velocity of high-affinity taurine uptake by the crude synaptosomal preparation was studied as a function of sodium and taurine concentration. Hill plots were constructed from these data. The requirement of high-affinity taurine uptake on a sodium gradient was examined by utilizing monensin, and the metabolic poisons, 2,4-dinitrophenol and ouabain. The major findings are as follows: 1) One sodium ion is co-transported with each taurine molecule; 2) the high-affinity uptake process is driven by the sodium concentration gradient across the membrane; 3) sodium increases the maximal velocity rather than the affinity of the high-affinity taurine carrier for the taurine molecule; 4) one taurine molecule is transported per carrier for both the high- and low-affinity taurine uptake systems; and 5) high-affinity taurine uptake is an energy-dependent process.

Successful ECT in a patient with hydrocephalus, shunt, hypopituitarism, and paraplegia.

A 25-year-old patient with paraplegia, hypopituitarism, hydrocephalus, and a ventriculoperitoneal shunt was successfully treated with a course of bilateral electroconvulsive therapy (ECT) for major depression. Brain imaging studies and neurology/ endocrinology consultations were obtained prior to the use of ECT. Throughout the course of ECT, his replacement hormonal therapy continued. Prior to each ECT, additional parenteral hydrocortisone was also administered. Consistent with the previously published reports, the patient did not experience any neurological deterioration. A brief review of the literature on the use of ECT in patients with panhypopituitarism, spinal cord injury, and hydrocephalus is presented.

Effects of intrahypothalamic kainic acid injection on taurine levels, binding and uptake.

The neurochemical effects of unilateral intrahypothalamic injection of kainic acid on taurine levels and synaptosomal uptake and binding of taurine were investigated. Seven days after the kainic acid injections, there were no changes in either taurine uptake or binding. However, taurine levels were significantly increased by 54% over the control contralateral side. These data are consistent with the hypothesis that taurine is localized in glial cells; the increased levels being a result of gliosis after kainic acid injections.

Successful ECT in a patient with intracranial venous angioma

The 1990 American Psychiatric Association (APA) Task Force report on electroconvulsive therapy (ECT) suggests that there is an increased risk of complications in patients with intracranial vascular masses. There have been only a few published reports on the use of ECT in these patients. In this case report, an additional case is described that used ECT in the treatment of major depression in a 72-year-old patient with a venous angioma involving the left cerebellum. Brain imaging studies, neurosurgery, cardiology, and orthopedic consultations were obtained prior to ECT. Blood pressure was monitored closely throughout the course of ECT. Prior to each ECT, antihypertensive medication was given in addition to other pretreatment medications. Consistent with previously published reports, the patient did not experience any neurological deterioration or adverse effects. A brief review of the literature on the use of ECT in patients with venous angioma and other intracranial vascular masses is presented.

A Model of the Compartmentalization of Taurine in Rat Hypothalamic Neuronal and Glial Cell Particles

We conclude that the high affinity taurine uptake system is located on neuronal membranes in the hypothalamus and that the low affinity taurine uptake system is located on glial membranes. The evoked release of taurine by either K+ and/or veratridine is Ca2+-independent and thus taurine, according to classical criteria, does not function as a neurotransmitter in the hypothalamus. This model for the differential cellular transport and compartmentalization of taurine into neuronal and glial cells and for a cytoplasmic location has important implications concerning its possible role in the central nervous system, specifically as a neuromodulator of neuronal activity.