PT  - JOURNAL ARTICLE
AU  - Kapusta, Daniel R.
AU  - Chang, Jaw-Kang
AU  - Kenigs, Velga A.
TI  - Central Administration of [Phe<sup>1</sup>Ψ(CH<sub>2</sub>-NH)Gly<sup>2</sup>]Nociceptin(1-13)-NH<sub>2</sub>and Orphanin FQ/Nociceptin (OFQ/N) Produce Similar Cardiovascular and Renal Responses in Conscious Rats
DP  - 1999 Apr 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 173--180
VI  - 289
IP  - 1
4099  - http://jpet.aspetjournals.org/content/289/1/173.short
4100  - http://jpet.aspetjournals.org/content/289/1/173.full
SO  - J Pharmacol Exp Ther1999 Apr 01; 289
AB  - In vitro studies have shown that [Phe1Ψ(CH2-NH)Gly2]OFQ/N(1–13)-NH2(referred to as [FG]OFQ/N(1–13)-NH2) is the first selective antagonist to prevent the binding of the endogenous ligand orphanin FQ/Nociceptin (OFQ/N) at the orphan opioid-like receptor. In the present study, we examined the potential changes in cardiovascular and renal function produced by the i.c.v. injection of [FG]OFQ/N(1–13)-NH2 in conscious Sprague-Dawley rats. In conscious rats, i.c.v. injection of [FG]OFQ/N(1–13)-NH2produced a marked and sustained decrease in heart rate, mean arterial pressure, and urinary sodium excretion and a profound increase in urine flow rate (i.e., a water diuresis). The cardiovascular and renal excretory responses produced by i.c.v. [FG]OFQ/N(1–13)-NH2 were dose dependent and were similar in pattern but of longer duration than responses evoked by i.c.v. OFQ/N. In other animals, the i.c.v. injection of OFQ/N(1–13)-NH2, a potential metabolite of [FG]OFQ/N(1–13)-NH2, produced changes in cardiovascular and renal function that were comparable to those evoked by i.c.v. [FG]OFQ/N(1–13)-NH2. In contrast, OFQ/N(2–17), a fragment of OFQ/N [OFQ/N(1–17)], was inactive when administered centrally. Finally, studies were performed to determine whether [FG]OFQ/N(1–13)-NH2 may be an antagonist at the orphan opioid-like receptor receptor when administered centrally at a dose that alone was inactive. In these studies, i.c.v. pretreatment of animals with low-dose [FG]OFQ/N(1–13)-NH2 failed to prevent the cardiovascular and renal excretory response to i.c.v. OFQ/N. Although [FG]OFQ/N(1–13)-NH2 is reported to be an antagonist of the OFQ/N receptor in vitro, these findings indicate that this compound has agonist activity similar to that of the endogenous ligand OFQ/N when administered centrally in vivo. The American Society for Pharmacology and Experimental Therapeutics