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Central Gαi and Gαo protein inhibition by pertussis toxin (PTX) blocks the cardiovascular depressor but not diuretic response to central Nociceptin/Orphanin FQ (N/OFQ) administration in conscious Sprague‐Dawley rats
Author(s) -
Wainford Richard D.,
Kurtz Kristine,
Kapusta Daniel R.
Publication year - 2007
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.21.6.a785-b
Subject(s) - nociceptin receptor , nop , diuretic , endocrinology , chemistry , medicine , vasopressin , opioid , pharmacology , opioid peptide , receptor
Intracerebroventricular (i.c.v.) injection of the opioid‐like peptide, nociceptin/Orphanin FQ (N/OFQ), produces cardiovascular (CV) depressor and diuretic responses in conscious rats via inhibition of central sympathetic outflow and vasopressin secretion, respectively. We examined if the CV and/or diuretic responses to central N/OFQ are mediated by a PTX‐sensitive Gαi/Gαo transducer protein pathway. Methods 48‐hrs prior to study, rats received i.c.v. injection of PTX (1 μg; N=4) or isotonic saline vehicle (5 μl; N=6). On the study day, N/OFQ was injected i.c.v. (5.5 nmol) in conscious chronically instrumented rats. Mean arterial pressure (MAP) and heart rate (HR) were recorded and urine collected for 80‐min (10‐min periods). Results I.c.v. N/OFQ failed to alter MAP (20‐min; PTX, Δ−1±3 mmHg; vehicle, Δ −16 ± 5 mmHg; P<0.05), or HR (PTX, Δ+12 ± 17 bpm; vehicle, Δ −82 ± 14 bpm; P<0.05) in rats pretreated centrally with PTX. In PTX and vehicle‐treated animals i.c.v. N/OFQ produced significant and comparable increases in urine flow rate (30‐min; PTX, 151 ± 20 μl/min; vehicle, 150 ± 13 μl/min). Conclusion Central PTX blocked the CV depressor but not diuretic response to i.c.v. N/OFQ. Thus, it appears N/OFQ activates central N/OFQ peptide (NOP) receptors that are differentially coupled to G‐protein pathways which are involved in the central neural control of CV function (Gαi/Gαo) versus the renal handling of water (possibly Gαz or Gαq) in conscious rats. DK43337, HL 071212, P20 RR018766