An analysis of unsurmountable antagonism to 5-hydroxytryptamine in the isolated perfused rat kidney: evidence for pseudoirreversible inhibition
Many 5-hydroxytryptamine (5-HT) antagonists give rise to unsurmountable antagonism. Unlike competitive antagonism, unsurmountable antagonism is not limited to a single mechanism, and therefore its utility for receptor identification, characterization, and classification is at best limited. In general, however, the mechanistic bases of unsurmountable antagonism have not received rigorous attention. The objectives of this chapter are to document instances of unsurmountable antagonism, to discuss possible mechanisms involved, and to present data suggesting that pseudoirreversible antagonism best explains unsurmountable antagonism of 5-HT-induced vasoconstriction in the isolated perfused rat kidney. Finally, the utility of antagonist probes for receptor classification will be discussed.
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