Differential sensitivity to phenoxybenzamine alkylation among types of neurokinin binding sites.

The effect of phenoxybenzamine (PBZ) treatment of crude membranes was examined on binding to neurokinin/tachykinin NK-1, NK-2, and NK-3 binding sites. PBZ in concentrations up to 300 microM resulted in only a slight reduction in Bmax in binding of iodinated substance P to NK-1 sites in rat submaxillary gland and in rat urinary bladder. PBZ in concentrations as low as 30 microM resulted in a decrease in Bmax or in affinity in binding of iodinated neurokinin A (substance K) to NK-2 sites in hamster bladder and in rat bladder, and a decrease in affinity in binding of iodinated eledoisin to NK-3 sites in rat cerebral cortex. The results indicate a parallelism in differential sensitivity to PBZ alkylation between neurokinin biological receptors and neurokinin ligand binding sites.