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Research ArticleArticle

Central Administration of [Phe1Ψ(CH2-NH)Gly2]Nociceptin(1-13)-NH2and Orphanin FQ/Nociceptin (OFQ/N) Produce Similar Cardiovascular and Renal Responses in Conscious Rats

Daniel R. Kapusta, Jaw-Kang Chang and Velga A. Kenigs
Journal of Pharmacology and Experimental Therapeutics April 1999, 289 (1) 173-180;
Daniel R. Kapusta
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Jaw-Kang Chang
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Velga A. Kenigs
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Abstract

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.

Footnotes

  • Send reprint requests to: Daniel R. Kapusta, Ph.D., Department of Pharmacology, Louisiana State University Medical Center, 1901 Perdido St., New Orleans, LA 70112. E-mail: dkapus{at}lsumc.edu

  • ↵1 This work was supported by National Institute of Diabetes and Digestive and Kidney Diseases Grant DK-43337 and American Heart Association, Louisiana Affiliate, Grant 91-6-08B (to D.R.K.).

  • Abbreviations:
    CNS
    central nervous system, OFQ/N, orphanin FQ/nociceptin, [FG]OFQ/N(1–13)-NH2, [Phe1Ψ(CH2-NH)Gly2]OFQ/N(1–13)-NH2, ORL1, opioid receptor-like 1
    • Received July 1, 1998.
    • Accepted November 4, 1998.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 289 (1)
Journal of Pharmacology and Experimental Therapeutics
Vol. 289, Issue 1
1 Apr 1999
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Research ArticleArticle

Central Administration of [Phe1Ψ(CH2-NH)Gly2]Nociceptin(1-13)-NH2and Orphanin FQ/Nociceptin (OFQ/N) Produce Similar Cardiovascular and Renal Responses in Conscious Rats

Daniel R. Kapusta, Jaw-Kang Chang and Velga A. Kenigs
Journal of Pharmacology and Experimental Therapeutics April 1, 1999, 289 (1) 173-180;

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Research ArticleArticle

Central Administration of [Phe1Ψ(CH2-NH)Gly2]Nociceptin(1-13)-NH2and Orphanin FQ/Nociceptin (OFQ/N) Produce Similar Cardiovascular and Renal Responses in Conscious Rats

Daniel R. Kapusta, Jaw-Kang Chang and Velga A. Kenigs
Journal of Pharmacology and Experimental Therapeutics April 1, 1999, 289 (1) 173-180;
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