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Effects of cations on binding, in membrane suspensions, of various opioids at μ‐sites of rabbit cerebellum and κ‐sites of guinea‐pig cerebellum
Author(s) -
Kosterlitz H.W.,
Paterson S.J.,
Robson L.E.,
Traynor J.R.
Publication year - 1987
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.1476-5381.1987.tb10298.x
Subject(s) - diprenorphine , chemistry , oxotremorine , (+) naloxone , enkephalin , agonist , guinea pig , endocrinology , medicine , dynorphin a , binding site , long term potentiation , choline chloride , cerebellum , antagonist , pharmacology , biochemistry , opioid , opioid peptide , receptor , biology
1 At the μ‐sites of rabbit cerebellum, NaC1, LiC1, KCl, choline chloride and MnCl 2 were tested for potentiation and inhibition of the binding of several opioids. Naloxone, (–)‐bremazocine and diprenorphine are μ‐antagonists in pharmacological assays and their binding is potentiated by the lower concentrations and inhibited by the higher concentrations of NaCl. The binding of the agonists [ 3 H]‐[ d ‐Ala 2 , MePhe 4 , Gly‐ol 5 ]enkephalin and [ 3 H]‐dihydromorphine is inhibited. MnCl 2 /potentiates the binding of the agonist [ 3 H]‐[ d ‐Ala 2 , MePhe 4 , Gly‐ol 5 ]enkephalin but not the binding of the antagonists. The thresholds of inhibition and slopes of the dose‐response curves for inhibition by MnCl 2 and LiCl vary. This finding may indicate that potentiating effects of MnCl 2 and LiCl are masked by simultaneous inhibition. 2 At the κ‐sites of guinea‐pig cerebellum, NaCl, KCl and MnCl 2 inhibit the binding of [ 3 H]‐dynorphin A (1–8), [ 3 H]‐dynorphin A (1–9), [ 3 H]‐(–)‐bremazocine, [ 3 H]‐tifluadom, and [ 3 H]‐diprenorphine. NaCl also causes a small potentiation of the binding of [ 3 H]‐diprenorphine, which is a κ‐agonist in the guinea‐pig myenteric plexus but a κ‐antagonist in the rabbit vas deferens. The slopes of the inhibitory dose‐response curves and the thresholds of inhibition vary with the different ligands. Therefore some potentiating effects may have been masked. 3 The results support the view that NaCl, and perhaps LiCl, but not KCl and choline chloride, potentiate the binding of μ‐antagonists but not the binding of μ‐agonists. It is not yet possible to decide whether, at the κ‐site, there is a similar differentiation of the binding of agonists and antagonists.