Alkylation with β‐funaltrexamine suggests differences between μ‐opioid receptor systems in guinea‐pig brain and myenteric‐plexus

Open Access
Publisher Website
Google Scholar
Abstract
1 The effects of pre-incubation with β-funaltrexamine (β-FNA) on the binding of [3H]-[d-Ala2, MePhe4, Gly-ol5]enkephalin ([3H]-DAMGO) to homogenates of guinea-pig brain and myenteric-plexus longitudinal muscle have been studied. 2 β-FNA pretreatment of brain homogenates in Tris-HCl buffer reduced the amount of [3H]-DAMGO binding. This was principally due to a reduction in the maximal number of binding sites measurable. However, approximately 30% of sites labelled by 1 nm [3H]-DAMGO were insensitive to 1 μm β-FNA. Similar findings were obtained when the alkylation was performed in brain homogenates prepared in Krebs solution buffered with HEPES. 3 β-FNA pretreatment of whole myenteric-plexus longitudinal muscle strips caused an increase in the IC50 values of μ-agonists, but not of κ-agonists. However, the binding of [3H]-DAMGO to homogenates of myenteric-plexus longitudinal muscle was not altered by pre-incubation with β-FNA in Tris-HCl buffer. On the other hand when the pretreatment was carried out in whole tissue in Krebs solution, or in homogenates in the presence of NaCl and Gpp(NH)p, a marked reduction in [3H]-DAMGO binding was observed. 4 These results suggest that a low affinity form of the μ-opioid receptor is the physiologically relevant site for β-FNA alkylation in the myenteric-plexus and that differences exist between μ-receptor systems in guinea-pig myenteric plexus and brain.