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Nociceptin/Orphanin FQ (N/OFQ) stimulated diuresis is mediated via inhibition of vasopressin secretion: a role for the hypothalamic paraventricular nucleus (PVN)
Author(s) -
Wainford Richard David,
Glatzer Nicholas R,
Tasker Jeffrey G,
Kapusta Daniel R
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.967.11
Subject(s) - nociceptin receptor , endocrinology , medicine , nop , vasopressin , chemistry , diuresis , diuretic , vasotocin , microinjection , receptor antagonist , receptor , antagonist , neuropeptide , kidney , opioid , opioid peptide
The role(s) of vasopressin (AVP) and the hypothalamic PVN in mediating the diuretic response to intracerebroventricular (i.c.v.) and PVN microinjection of N/OFQ was examined in rats. Methods N/OFQ was injected i.c.v. (5.5 nmol) in conscious instrumented Sprague‐Dawley rats (n=6/group) infused i.v. with isotonic saline (50 μl/min), AVP (170 pg/kg/min) or a V2‐ AVP receptor antagonist (10 nmol/kg/hr) and urine was collected for 80‐min (10‐min periods). In other studies, blood was collected 10‐min post‐i.c.v. or PVN (100 pmol) N/OFQ injection and assayed for AVP. N/OFQ peptide (NOP) receptor immunohistochemistry (IHC) was performed in rat brains expressing GFP in AVP neurons. Results I.c.v. and PVN injection of N/OFQ produced a profound diuresis (PVN N/OFQ peak diuresis; 40‐min, Δ164±22 μl/min, P<0.05) in rats. I.v. infusion of a V2‐receptor antagonist increased basal urine output and prevented a further i.c.v. N/OFQ‐induced diuresis. I.v. infusion of AVP reduced basal urine output and prevented the diuretic response to i.c.v. N/OFQ. In naïve rats, 10‐min post‐i.c.v. or PVN N/OFQ, plasma AVP levels were significantly reduced (i.c.v. vehicle, 2.2±0.2 pg/ml; i.c.v. N/OFQ, 1.4±0.1; PVN N/OFQ, 1.3±0.1 P<0.05). IHC studies demonstrated the presence of NOP receptors on AVP expressing PVN magnocellular neurons. Conclusion In conscious rats, N/OFQ acts within the PVN, likely at the level of magnocellular neurons, to suppress AVP secretion and thereby produce diuresis. Supported by DK43337, HL 071212, AHA 0855293E, P20 RR018766 to DRK and NS042081 (JGT).