No abstract

Ion channels were studied using the whole-cell patch clamp technique in bovine retinal and choroidal microvascular endothelial cells (MVEC) cultured under the same conditions. The two types of MVEC expressed inward currents at hyperpolarizing voltage steps and showed small outward currents at depolarizing steps. The extrapolated reversal potentials of the inward currents were near to the potassium equilibrium potential. Cs⁺ and the K⁺ channel blocker TEA reduced the amplitudes of the currents indicating the selectivity and permeability for potassium. This was confirmed by changes of outside K⁺ concentration shifting the I-V curves to the right. RT-PCR studies revealed the presence of mRNA of Kir2.1, an inwardly rectifying K⁺ channel, in retinal and choroidal MVEC. The profile of the small outward currents is related to the Kv family but not identical with the Kv1.4 subtype.

Adenosine, which is released under pathophysiological conditions such as hypoxia or ischemia, is involved in a variety of regulatory processes related to neuroprotection. Major advances in the research on neuronal adenosine receptors have provided a better understanding of the mechanisms underlying the neuroprotective effects during hypoxia. The therapeutic potential of adenosine was recognized several years ago, but only the development of stable and selective adenosine receptor agonists and antagonists has offered novel approaches for the pharmacological manipulation of the receptor activity. To date, four G protein coupled receptors have been cloned and identified in the central nervous system: A 1 , A 2A , A 2B , and A 3. The neuroprotective effects of adenosine are mediated primarily by the activation of A 1 receptors. Knowledge of the physiological role of A 3 receptors in the brain is still limited. This article focuses on new evidences referring to possible functions of A 3 receptors in the CNS, especially the role during hypoxia. Electrophysiological investigations on brain slices give us new insights concerning mechanisms of synaptic modulation. The data from pyramidal cells of the rat cingulate cortex show that a high level of endogenous adenosine (occuring during hypoxia) activates A 3 receptors, which mediates a depression of the synaptic transmission. The A 3 receptors inhibit the glutamate release additionally to and independently from the A 1 receptors. The two distinct mechanisms of synaptic modulation contribute to the neuroprotective action of adenosine during hypoxia and offer new approaches for therapeutic strategies. Drug Dev. Res. 58:420-427, 2003.

Patients with functional gastrointestinal disorders constitute the majority of patients seeking healthcare for gastrointestinal symptoms in primary and secondary care. Of these disorders irritable bowel syndrome (IBS) is one of the most common and affects 10-20% in the Western world. IBS is a functional bowel disorder characterized by chronic abdominal pain, discomfort, bloating, and alteration of bowel habits in the absence of any detectable organic cause. Sex and gender aspects are important in understanding differences between men and women in their risk and experience of IBS. Relative to men, women are diagnosed more frequently with IBS. Female patients are more likely to be constipated, complain of abdominal distension and of certain extracolonic symptoms. Given the variability of IBS, the most successful treatment will be comprehensive, involving multiple strategies. Efficacy, safety and tolerability are important in the evaluation of IBS therapies, as patients are likely to require long-term treatment. Laxatives, antidiarrheals or antispasmodics are common in the treatment of IBS but the majority of patients receive antispasmodics followed by prokinetic agents. In treatment of IBS there appears to be a greater clinical response to serotonergic agents developed for IBS in women compared to men. There is an absence of drugs licensed specifically for the treatment of IBS. Further studies with novel agents are needed, to evaluate new approaches to IBS management including gender specific behavioral therapies and better characterization of patient subgroups with regard to drug therapy so that personalized therapy can be tested.