Polyamines non-competitively inhibit [3H]3-PPP binding to sigma receptors
1990; Elsevier BV; Volume: 184; Issue: 1 Linguagem: Inglês
10.1016/0014-2999(90)90685-y
ISSN1879-0712
AutoresIan A. Paul, Gemma Kuypers, Moussa B. H. Youdim, Phil Skolnick,
Tópico(s)Phenothiazines and Benzothiazines Synthesis and Activities
ResumoDesipramine, imipramine, clomipramine, (−)-propranolol, (−)-alprenolol, (±)-pentazocine and risperidone caused a concentration-dependent inhibition of 6 nM [3H]DTG (1,3-di-o-tolylguanidine)-defined sigma (σ) binding with Ki values of about 0.5–2.5 μM in well-washed homogenates obtained from rat cerebral cortex. The saturation studies revealed that the inhibition by desipramine (1–4 μM), (−)-propranolol (1 μM) and (−)-alprenolol (3 μM) resulted from a reduction of the Bmax value without alteration of the Kd of [3H]DTG binding to the cortex or hippocampus. In contrast, imipramine, (±)-pentazocine, clomipramine and risperidone competitively attenuated the cortical or hippocampal [3H]DTG binding. These findings demonstrate the uncompetitive inhibition of [3H]DTG binding by neuroactive drugs, thereby providing further support for the possible multiple regulation of cerebral σ receptors.
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