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Retinal pericytes are key cells involved in the regulation of retinal blood flow. The purpose of this work was to identify the K+ channel population expressed in cultured bovine retinal pericytes and to determine whether beta-adrenergic stimulation alters the activity of these channels. Isolated pericytes were obtained by homogenization and filtration of bovine retina and K+ channels were studied with the whole-cell configuration of the patch-clamp technique on 3-5 passaged pericytes. Pericytes expressed an inward current dependent on extracellular K+ concentration which was sensitive to micromolar concentrations of barium, a characteristic of an inward-rectifying K+ current. Furthermore, two voltage-dependent outward currents were also observed. Their activation and inactivation properties, as well as their respective sensitivity to 4-aminopyridine and iberiotoxin, were indicative of voltage-sensitive and large-conductance calcium-activated K+ channels (BKCa). Isoproterenol and dibutyryl cyclic adenosine monophosphate enhanced the activity of BKCa without affecting the other potassium currents. In conclusion, bovine retinal pericytes express mainly two outward potassium currents, KV and BKCa, as well as an inward rectifying K+ current, Kir. Physiologic stimuli such as an increase in extracellular potassium concentration or beta-adrenergic receptor stimulation enhance the activity of Kir and BKCa, respectively, suggesting a potential role for these channels in the control of retinal blood flow.

Aim: To determine in the hamster cheek pouch whether or not the changes in plasma extravasation induced by vascular endothelial growth factor (VEGF) could be affected by fructose diet., Methods: Hamsters were subjected to control drinking water or to water containing fructose (10 %) for 18 weeks., Results: The fructose diet induced a small but significant increase in glycemia (0.80+/-0.11 and 1.09+/-0.15, n=8 and 9 for control and fructose- treated animals, respectively, P<0.05). Bradykinin-induced plasma extravasation was not affected by the fructose diet while the effects of VEGF were markedly increased (maximal number of leakage sites: 76+/-20 and 126+/-55, n = 8 and 9 for control and fructose-treated animals, respectively, P<0.01)., Conclusion: Even moderate changes in glycemic levels can produce profound alteration in the VEGF response.

Melanin-concentrating hormone (MCH) is a cyclic neuropeptide, with a major role in stimulation of feeding behavior in mammals. MCH signals in the brain occur via two seven-transmembrane G protein-coupled receptors, namely MCH1 (SLC-1, MCH(1), MCH-R1, or MCH-1R) and MCH2 (SLT, MCH(2), MCH-R2, or MCH-2R). In this study, we demonstrate that the pro-MCH(131-165) peptide neuropeptide-glutamic acid-isoleucine (NEI)-MCH is more potent than MCH in stimulating feeding in the rat. Using rat MCH1-expressed human embryonic kidney 293 cells, we show that NEI-MCH exhibits 5-fold less affinity in a binding assay and 2-fold less potency in a cAMP assay than MCH. A similar 7- to 8-fold shift in potency was observed in a Ca(2+)(i) assay using rat MCH1 or human MCH2-transfected Chinese hamster ovary cell models. This demonstrates that NEI-MCH is not a better agonist than MCH at either of the MCH receptors. Then, we compared the proteolysis resistance of MCH and NEI-MCH to rat brain membrane homogenates and purified proteases. Kinetics of peptide degradation using brain extracts indicated a t(1/2) of 34.8 min for MCH and 78.5 min for NEI-MCH with a specific pattern of cleavage of MCH but not NEI-MCH by exo- and endo-proteases. Furthermore, MCH was found highly susceptible to degradation by aminopeptidase M and endopeptidase 24.11, whereas NEI-MCH was fully resistant to proteolysis by these enzymes. Therefore, our results strongly suggest that reduced susceptibility to proteases of NEI-MCH compared with MCH account for its enhanced activity in feeding behavior. NEI-MCH represents therefore the first MCH natural functional "superagonist" so far described.

Chronic stress is now the commonest contributor to ill health in modern societies. The cost of stress in terms of absenteeism, lost productivity, and health care expense is rapidly increasing. As the problem continues to worsen, there will be an increasing need for interactive systems designed to help people cope with stress. Effective prevention of stress's adverse effects will require the widest possible deployment and implementation of stress reduction strategies., (Copyright 2002, Elsevier Science (USA). All rights reserved.)