A reassessment of the binding of [3H]rauwolscine to membranes from the rat cortex.
In order to fully resolve the binding profile of [3H]rauwolscine to membranes from the cortex of the rat, saturation, competition and association-dissociation data were analysed by means of computerised curve-fitting techniques. The binding isotherm for [3H]rauwolscine was best fitted to a two-component model consisting of a high-affinity, saturable site (approx. Kd 1.8 nM) and a low-affinity, apparently non-saturable, component. Displacement experiments revealed shallow inhibition curves for both antagonist and agonist ligands with a rank order of potency indicative of an interaction at the alpha 2-adrenoceptor. Inclusion of spiroperidol, but not prazosin, markedly steepened the antagonist, but not the agonist inhibition curves. In addition, spiroperidol attenuated, but did not eliminate, the low-affinity component in saturation experiments. Dissociation and association data revealed a biphasic paradigm, the more slowly-associating/dissociating component of which was sensitive to spiroperidol. It was concluded that [3H]rauwolscine binds to two sites on membranes of the rat cortex; a high-affinity site corresponding to alpha 2-adrenoceptors and a low-affinity, spiroperidol-sensitive component. The possible identity of the low-affinity site is discussed with particular emphasis on displacement data for [3H]rauwolscine and the interaction with rauwolscine in isolated organs.
Broadhurst
A M
AM
Wyllie
M G
MG
D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D002540:Cerebral Cortex / Q000378:metabolism*; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D008566:Membranes / Q000378:metabolism; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013134:Spiperone / Q000494:pharmacology; D015016:Yohimbine / Q000378:metabolism*
D015016:Yohimbine; D013134:Spiperone; D011224:Prazosin