title: Norepinephrine reduces ω-conotoxin-sensitive Ca2+ currents in renal afferent neurons in rats.
abstract: Sympathetic efferent and peptidergic afferent renal nerves likely influence hypertensive and inflammatory kidney disease. Our recent investigation with confocal microscopy revealed that in the kidney sympathetic nerve endings are colocalized with afferent nerve fibers (Ditting T, Tiegs G, Rodionova K, Reeh PW, Neuhuber W, Freisinger W, Veelken R. Am J Physiol Renal Physiol 297: F1427-F1434, 2009; Veelken R, Vogel EM, Hilgers K, Amman K, Hartner A, Sass G, Neuhuber W, Tiegs G. J Am Soc Nephrol 19: 1371-1378, 2008). However, it is not known whether renal afferent nerves are influenced by sympathetic nerve activity. We tested the hypothesis that norepinephrine (NE) influences voltage-gated Ca(2+) channel currents in cultured renal dorsal root ganglion (DRG) neurons, i.e., the first-order neuron of the renal afferent pathway. DRG neurons (T11-L2) retrogradely labeled from the kidney and subsequently cultured, were investigated by whole-cell patch clamp. Voltage-gated calcium channels (VGCC) were investigated by voltage ramps (-100 to +80 mV, 300 ms, every 20 s). NE and appropriate adrenergic receptor antagonists were administered by microperfusion. NE (20 μM) reduced VGCC-mediated currents by 10.4 ± 3.0% (P < 0.01). This reduction was abolished by the α-adrenoreceptor inhibitor phentolamine and the α(2)-adrenoceptor antagonist yohimbine. The β-adrenoreceptor antagonist propranolol and the α(1)-adrenoceptor antagonist prazosin had no effect. The inhibitory effect of NE was abolished when N-type currents were blocked by ω-conotoxin GVIA, but was unaffected by other specific Ca(2+) channel inhibitors (ω-agatoxin IVA; nimodipine). Confocal microscopy revealed sympathetic innervation of DRGs and confirmed colocalization of afferent and efferent fibers within in the kidney. Hence NE released from intrarenal sympathetic nerve endings, or sympathetic fibers within the DRGs, or even circulating catecholamines, may influence the activity of peptidergic afferent nerve fibers through N-type Ca(2+) channels via an α(2)-adrenoceptor-dependent mechanism. However, the exact site and the functional role of this interaction remains to be elucidated.
authors: Dept. of Internal Medicine 4, Nephrology and Hypertension, Erlangen, Germany. tilmann.ditting@uk-erlangen.de
authors: Tilmann
authors: T
authors: Ditting
authors: Peter
authors: P
authors: Linz
authors: Wolfgang
authors: W
authors: Freisinger
authors: Sonja
authors: S
authors: Heinlein
authors: Peter W
authors: PW
authors: Reeh
authors: Christian
authors: C
authors: Fiedler
authors: Kirsten
authors: K
authors: Siegel
authors: Karie E
authors: KE
authors: Scrogin
authors: Winfried
authors: W
authors: Neuhuber
authors: Roland
authors: R
authors: Veelken
mesh_terms: D058669:Adrenergic alpha-2 Receptor Antagonists / Q000494:pharmacology; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000502:physiology*; D002478:Cells, Cultured; D004347:Drug Interactions; D005727:Ganglia, Spinal / Q000166:cytology / Q000502:physiology; D007668:Kidney / Q000294:innervation*; D008297:Male; D009475:Neurons, Afferent / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D009638:Norepinephrine / Q000494:pharmacology*; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D018341:Receptors, Adrenergic, alpha-2 / Q000502:physiology; D017779:Sympathetic Fibers, Postganglionic / Q000187:drug effects / Q000502:physiology; D015016:Yohimbine / Q000494:pharmacology; D020960:omega-Conotoxins / Q000494:pharmacology*
chemical_list: D058669:Adrenergic alpha-2 Receptor Antagonists; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D018341:Receptors, Adrenergic, alpha-2; D020960:omega-Conotoxins; D015016:Yohimbine; D009638:Norepinephrine