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Pre‐incubation of guinea‐pig myenteric plexus with β‐funaltrexamine: discrepancy between binding assays and bioassays
Author(s) -
Corbett A.D.,
Kosterlitz H.W.,
McKnight A.T.,
Paterson S.J.,
Robson L.E.
Publication year - 1985
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1985.tb10562.x
Subject(s) - myenteric plexus , guinea pig , chemistry , agonist , enkephalin , receptor , binding site , pharmacology , potency , ligand (biochemistry) , in vitro , biochemistry , stereochemistry , medicine , endocrinology , biology , opioid , immunohistochemistry
1 The acute effects of β‐funaltrexamine and the effects of pre‐incubation with this compound were examined in five in vitro assay tissues and in selective binding assays in homogenates of guinea‐pig brain and myenteric plexus. 2 In competitive displacement assays with selective ligands, β‐funaltrexamine had highest affinity for the μ‐binding site in the myenteric plexus and brain of guinea‐pig. Its affinity for the k‐site was about 15% of that for the μ‐site. 3 Pre‐incubation of the assay tissues with β‐funaltrexamine caused an increase in the IC 50 values of μ‐and δ‐receptor agonists but not of k‐agonists. Although in bioassays on the myenteric plexus‐longitudinal muscle preparation of the guinea‐pig, the IC 50 value of the μ‐receptor ligand [D‐Ala 2 , MePhe 4 , Gly‐ol 5 ] enkephalin was increased up to 124 fold, its binding at the μ‐site in homogenates of the preparation was not affected by this treatment. 4 These findings indicate that the effects of pre‐incubation with β‐funaltrexamine on agonist potency of the μ‐receptor ligand are due to an interference with the coupling mechanism between the μ‐binding site and the effector system.