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Sympathetic Nerve Varicosities in Close Apposition to Basolateral Membranes of Collecting Duct Epithelial Cells of Rat Kidney

Loesch A.a · Unwin R.b · Gandhi V.a · Burnstock G.c
aResearch Department of Inflammation, bCentre for Nephrology (London Epithelial Group), and cAutonomic Neuroscience Centre, UCL Medical School, Royal Free Campus, London, UK Nephron Physiol 2009;113:p15–p21 (DOI:10.1159/000235246)


Background: There are reports of sympathetic innervation of the nephron and of P2 purinergic receptors on epithelial cells. Since ATP is a cotransmitter with noradrenaline in sympathetic nerves, the objective of the present study was to re-investigate basolateral innervation of rat renal collecting duct epithelial cells by sympathetic nerves in the context of recent data on the effects of ATP on this nephron segment. Methods: Kidney sections were processed for electron immunocytochemistry, using tyrosine hydroxylase rabbit polyclonal antibody, with a second layer of biotinylated donkey anti-rabbit antibody and finally extravidin-horseradish peroxidase. Immunoreactivity was visualised with 3,3′-diaminobenzidine and examined with a Philips CM120 transmission electron microscope. Results: Electron microscopic evidence is presented for close apposition of sympathetic nerve varicosities immunolabelled with tyrosine hydroxylase to principal and intercalated type epithelial cells of the collecting duct of the cortical region. Conclusions: It is suggested that ATP is released as a cotransmitter from sympathetic nerve varicosities to act on basolateral P2 purinoceptors to influence sodium and water (and potentially acid-base) transport, in conjunction with the known (typically inhibitory) actions of autocrine and/or paracrine release of ATP from collecting duct epithelial cells acting via luminal P2 receptors. It is suggested that while luminal responses may dominate under normal physiological conditions, in pathophysiological states, such as stress and dehydration, sympathetic nerves might also be involved in modulating collecting duct fluid and electrolyte transport.


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