A guinea pig ileum preparation devoid of functional κ receptors: A new in vitro pharmacologic assay for μ-opioid ligands

Robert W. Schwartz, An Chih Chang, Philip S. Portoghese, Ilona P. Berzetei-Gurske

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Guinea pig ileum longitudinal muscle/myenteric plexus preparations contain functional μ- and κ-opioid receptors. A preparation with blocked κ receptors was obtained by pretreating guinea pigs with 0.1-10.0 mg/kg intraperitoneal doses of a new κ-selective affinity label, DIPPA (2-(3,4-dichlorophenyl)-N-methyl-N-[1S-1-(3-isothiocyanatophenyl)-2-(- 1-pyrrolidinyl) ethyl] acetamide). Determination of IC50 values for the μ-selective agonist DAMGO ([D-Ala2,MePhe4,Gly(ol)5]-enkephalin) and the κ-selective agonist U 69,593 ([5α,7α,8β]-(+)-N-methyl-N-[7-(1-pyrrolidinyl)-1-oxaspiro-(4,5)-dec -8-yl]) showed that 0.5 mg/kg DIPPA at 48 h produced reliable, near-complete blockade of κ-opioid activity but a minimal shift for μ-opioid agonism. This new assay should be useful for studying mixed agonists/antagonists that produce strong κ-opioid receptor agonism, which prevents determination of μ-opioid receptor antagonism.

Original languageEnglish (US)
Pages (from-to)PL-235-PL-239
JournalLife Sciences
Volume60
Issue number15
StatePublished - Mar 7 1997

Keywords

  • DIPPA
  • guinea pig ileum
  • κ-opioid receptor blockade

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