Neurophysiology of micturition and continence in women

Micturition and continence involve the coordination of complex neural events between the central and peripheral nervous systems. An understanding of these events provides a foundation for the treatment of voiding disorders in women such as stress urinary incontinence, urge incontinence and interstitial cystitis. The purpose of this paper is to comprehensively review the neuroanatomy, enurophysiology and neuropharmacology of micturition and continence. However, a brief section discussing clinical correlations will follow each of these topics to help integrate the basic science with clinical obervations.     

How Important Are Brain Banks for Alcohol Research?

This article contains the proceedings of a symposium at the 2002 RSA/ISBRA Meeting in San Francisco, organized and chaired by Clive Harper and co-chaired by Izuru Matsumoto. The presentations were (1) Introduction, by Clive Harper; (2) The quality of tissue-a critical issue, by Therese Garrick; (3) The first systematic brain tissue donor program in Japan, by Izuru Matsumoto; (4) Brain scans after death-really! by Adolf Pfefferbaum, Elfar Adalsteinsson, and Edith Sullivan; (5) Capture that (genial) expression, by Joanne Lewohl and Peter Dodd; and (6) Neurochemical/pharmacological studies: experimental design and limitations, by Roger Butterworth.     

Compared properties of central and peripheral binding sites for phencyclidine

Phencyclidine and its derivatives bind specifically and reversibly to rat brain and peripheral organs. Binding characteristics are different in brain, lung, kidney, heart and liver. Affinities of phencyclidines for the brain receptor but not those for peripheral organs are correlated with the pharmacological activities of phencyclidines as measured in the rotarod test.     

TMT-induced autonomic and behavioral changes and the neural basis of its processing

One of the main interests in the field of neuroscience is the investigation of the neural basis of fear. During recent years, an increasing number of studies have used trimethylthiazoline (TMT), a component of red fox feces, as a stimulus to induce fear in predator naive rats, mice, and voles. The aim of the present review is to summarize these studies. We present an overview to the autonomic and behavioral changes that are induced by TMT exposure. Then, we summarize the small number of studies that have examined the neural processing of the TMT stimulus. Finally, we compare these studies with those using a natural predator or predator odor to induce fear and discuss the possible use of TMT exposure in rodents as an animal model of unconditioned fear in humans.     

Drug binding to aromatic residues in the HERG channel pore cavity as possible explanation for acquired Long QT syndrome by antiparkinsonian drug budipine

Budipine is a non-dopaminergic antiparkinsonian drug causing acquired forms of Long QT syndrome (aLQTS). As a consequence, the manufacturer has restricted the use of budipine in patients who exhibit additional risk factors for the development of Torsades-de-Pointes tachycardias (TdP). The molecular basis of this serious side effect has not been elucidated yet.Human ether-a-go-go related gene (HERG) channel block being the main cause of drug induced QT prolongation, we investigated the effect of budipine on the rapid component of the delayed-rectifier potassium current (I_K(r)) in guinea pig cardiomyocytes and on HERG potassium channels heterologously expressed in Xenopus oocytes.In guinea pig cardiomyocytes, budipine (10 M) inhibited I_K(r) by 86% but was without any effect on calcium currents. In Xenopus oocytes, HERG potassium channels were blocked by budipine with an IC₅₀ of 10.2 M. Onset of block was fast and block was only slowly and incompletely reversible upon washout.Budipine blocked HERG channels in the open and inactivated state, but not in the closed states. The half-maximal activation voltage was slightly shifted towards more negative potentials. Steady-state inactivation of HERG was also influenced by budipine. Budipine block was neither voltage- nor frequency-dependent.In HERG channel mutants Y652A and F656A, drug affinity was reduced dramatically. Therefore, these two aromatic residues in the channel pore are likely to form a main part of the binding site for budipine.In summary, this is the first study that provides a molecular basis for the budipine-associated aLQTS observed in clinical practice. Furthermore, these findings underline the importance of the aromatic residues Y652 and F656 in the binding of lipophilic drugs to HERG channels.Abbreviations I_K(r) The rapid component of the delayed-rectifier potassium current - HERG Human ether-a-go-go related gene - aLQTS Acquired Long QT syndrome - TdP Torsade-de-Pointes tachycardia E.P. Scholz and E. Zitron contributed equally to this work     

Neuropharmacology of emesis and its relevance to anti-emetic therapy

 Recent great advances in the neuropharmacology of the emetic pathways have led to better therapy and improved insight into pathophysiological processes in patients undergoing chemo- and radiotherapy. This article gives an overview of the area, outlines current controversies and makes recommendations for future clinical studies.     

Attenuation of morphine tolerance development by electroconvulsive shock in mice

The development of tolerance to morphine has been proposed as being analogous to learning or memory, since the presentation of a novel stimulus (morphine) to an organism results in an altered response on subsequent presentations of the same stimulus. Electroconvulsive shock has been widely used to disrupt memory in animals and its effect on the development of tolerance to morphine was examined. Pretreatment of mice with six, progressively increasing intraperitoneal doses of morphine induced tolerance to an excitant action of morphine, shown by a marked reduction in the locomotor activity elicited by a subsequent intraperitoneal test dose of morphine. In three separate experiments, the administration of eleetroconvulsive shock 2–3 hr after each pretreatment with morphine attenuated the degree of tolerance developed. The eleetroconvulsive shock had no significant effect on the locomotor activity of non-tolerant mice tested under similar conditions in each experiment. In a single pilot study, electroconvulsive shock was found to reduce the frequency of jumping precipitated by an intraperitoneal dose of naloxone, suggesting a possible decrease in the degree of dependence. The present results are interpreted as supporting the view that the mechanisms of morphine tolerance may be similar to those involved in learning or memory.     

Monoamine oxidase type a: differences in selectivity towards l-norepinephrine compared to serotonin

l-Norepinephirine and serotonin have been regarded as preferential substrates for monoamine oxidase (MAO) type A. A close comparative examination of a number of tissues from different species, however, indicated the following differences. Serotonin was a more selective substrate for MAO-A, being inhibited by low concentrations (< 10^-7M) of the irreversible MAO-A inhibitor, clorgyline, more consistently and to a greater extent (80–100%) than was l-norepinephrine (30–85%). These serotonin-norepinephrine differences were greater in humans and other primates than in rodents. Serotonin also had a 2- to 4-fold smaller apparent K_m for MAO-A than l-norepinephrine and was deaminated 2- to 5-fold more readily by MAO in vitro in most tissues. In contrast, the MAO-B in human platelets deaminated l-norepinephrine more readily than serotonin. Thus, l-norepinephrine, like dopamine, should be regarded as a substrate for both MAO-A and MAO-B in vitro. The prominent role of MAO-B in norepinephrine degradation in primates may need to be considered in interpreting laboratory and clinical studies of clorgyline selective MAO-inhibiting drugs.