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Modulation of Ca2+ channels by opioid receptor-like 1 receptors natively expressed in rat stellate ganglion neurons innervating cardiac muscle.

Authors: Ruiz-Velasco, V  Puhl, HL  Fuller, BC  Sumner, AD 
Citation: Ruiz-Velasco V, etal., J Pharmacol Exp Ther. 2005 Sep;314(3):987-94. Epub 2005 Jun 3.
Pubmed: (View Article at PubMed) PMID:15937148
DOI: Full-text: DOI:10.1124/jpet.105.089284

Postganglionic sympathetic nerve terminals innervate cardiac muscle and express opioid receptor-like 1 (ORL1) receptors, the most recently described member of the opioid receptor subclass. ORL1 receptors are stimulated by the endogenous heptadecapeptide nociceptin (Noc). To better understand how the signaling events by Noc regulate sympathetic neuron excitability, the goal of the present study was to determine whether sympathetic stellate ganglion (SG) neurons, innervating the heart, natively express ORL1 opioid receptors and couple to Ca(2+) channels. SG neurons in adult male rats were retrograde-labeled with a fluorescent tracer via injection of the ventricular muscle employing ultrasound imaging. Thereafter, N-type Ca(2+) channel modulation was investigated using the whole-cell variant of the patch-clamp technique. Exposure of labeled SG neurons to Noc resulted in a concentration-dependent inhibition of Ca(2+) currents (with an estimated EC(50) of 193 +/- 14 nM). Pre-exposure of SG neurons to the ORL1 receptor blocker, [Nphe(1),Arg(14),Lys(15)]N/OFQ-NH(2) (UFP-101), significantly decreased the Noc-mediated Ca(2+) current inhibition. The Ca(2+) current inhibition was also blocked by pertussis toxin pretreatment, indicating that signaling occurs via Galpha(i/o) G proteins. Finally, the full-length ORL1 receptor cDNA in SG neurons was cloned and sequenced. Of the two known alternatively spliced variants in rats, sequencing analysis showed that the ORL1 receptor expressed in SG neurons is the short form. Overall, these results suggest that stimulation of postsynaptic ORL1 receptors by Noc in SG neurons regulate cardiac sympathetic activity.

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RGD ID: 9835002
Created: 2015-03-12
Species: All species
Last Modified: 2015-03-12
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.