Morphine-receptor dissociation constant and the stimulus-effect relation for inhibition of gastrointestinal transit in the rat

Robert B. Raffa, Frank Porreca, Alan Cowan, Ronald J. Tallarida

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

The dissociation constant (KA) of morphine for its receptor was determined by the method of partial irreversible blockade of the receptor population using inhibition of gastrointestinal transit of a forced charcoal meal as the pharmacological endpoint. The anti-motility effects of morphine was antagonized when rats were pretreated with buprenorphine (0.3 mg/kg s.c.), a narcotic antagonist analgesic, 30 min before morphine and the extent of gastrointestinal transit was estimated a further 45 min later. With this schedule of drug administration, the agonist action of buprenorphine is minimal and its antagonist action predominates. The value of KA was (1.1±0.2)×10-5 mol/kg, a value close to that previously reported (2.9×10-5 mol/kg) by us with these compounds in the rat tail flick test. The value of [A50] found here was 2.15×10-6 mol/kg, approximately 1 5 of that of KA. Also, the stimulus-effect relation of the tissue, defined in Stephenson's theory, was plotted and found to be nonlinear. This result, when coupled with the inequality of KA and [A50], argues against the application of classical drug-receptor theory to this system. The apparent agreement between KA values for anticiception and inhibition of gastrointestinal transit is interesting, but does not necessarily prove equivalent receptors mediating the two different effects.

Original languageEnglish (US)
Pages (from-to)11-16
Number of pages6
JournalEuropean Journal of Pharmacology
Volume79
Issue number1-2
DOIs
StatePublished - Apr 8 1982
Externally publishedYes

Keywords

  • Buprenorphine Gastrointestinal transit
  • Dissociation constant
  • Morphine K
  • Partial irreversible blockade
  • Stimulus-effect relation

ASJC Scopus subject areas

  • Pharmacology

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