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Endocrinology, doi:10.1210/en.2008-0178
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Endocrinology Vol. 149, No. 12 6136-6145
Copyright © 2008 by The Endocrine Society

The Effects of Apelin on the Electrical Activity of Hypothalamic Magnocellular Vasopressin and Oxytocin Neurons and Somatodendritic Peptide Release

Vicky A. Tobin, Philip M. Bull, Sathya Arunachalam, Anne-Marie O'Carroll, Yoichi Ueta and Mike Ludwig

Centre for Integrative Physiology (V.A.T., P.M.B., S.A., M.L.), University of Edinburgh, Edinburgh EH8 9XD, United Kingdom; Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology (A.-M.O'C.), University of Bristol, Bristol BS1 3NY, United Kingdom; and Department of Physiology (Y.U.), School of Medicine, University of Occupational and Environmental Health, Kitakyushu 807-8555, Japan

Address all correspondence and requests for reprints to: Mike Ludwig, Ph.D., Centre for Integrative Physiology, University of Edinburgh, George Square, Edinburgh EH8 9XD, United Kingdom. E-mail: mike.ludwig{at}ed.ac.uk.

Apelin, a novel peptide originally isolated from bovine stomach tissue extracts, is widely but selectively distributed throughout the nervous system. Vasopressin and oxytocin are synthesized in the magnocellular neurons of the hypothalamic supraoptic nucleus (SON) and paraventricular nucleus, which are apelin-rich regions in the central nervous system. We made extracellular electrophysiological recordings from the transpharyngeally exposed SON of urethane-anaesthetized rats to assess the role of apelin in the control of the firing activity of identified magnocellular vasopressin and oxytocin neurons in vivo. Apelin-13 administration onto SON neurons via microdialysis revealed cell-specific responses; apelin-13 increased the firing rates of vasopressin cells but had no effect on the firing rate of oxytocin neurons. A direct excitatory effect of apelin-13 on vasopressin cell activity is also supported by our in vitro studies showing depolarization of membrane potential and increase in action potential firing. To assess the effects of apelin-13 on somatodendritic peptide release, we used in vitro release studies from SON explants in combination with highly sensitive and specific RIA. Apelin-13 decreases basal (by 78%; P < 0.05; n = 6) and potassium-stimulated (by 57%; P < 0.05; n = 6) vasopressin release but had no effect on somatodendritic oxytocin release. Taken together, our data suggest a local autocrine feedback action of apelin on magnocellular vasopressin neurons. Furthermore, these data show a marked dissociation between axonal and dendritic vasopressin release with a decrease in somatodendritic release but an increase in electrical activity at the cell bodies, indicating that release from these two compartments can be regulated wholly independently.




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