Relative Selectivity of Plant Cardenolides for Na+/K+-ATPases From the Monarch Butterfly and Non-resistant Insects

Abstract

A major prediction of coevolutionary theory is that plants may target particular herbivores with secondary compounds that are selectively defensive. The highly specialized monarch butterfly (<i>Danaus plexippus</i>) copes well with cardiac glycosides (inhibitors of animal Na⁺/K⁺-ATPases) from its milkweed host plants, but selective inhibition of its Na⁺/K⁺-ATPase by different compounds has not been previously tested. We applied 17 cardiac glycosides to the <i>D. plexippus</i>-Na⁺/K⁺-ATPase and to the more susceptible Na⁺/K⁺-ATPases of two non-adapted insects (<i>Euploea core</i> and <i>Schistocerca gregaria</i>). Structural features (e.g., sugar residues) predicted <i>in vitro</i> inhibitory activity and comparison of insect Na⁺/K⁺-ATPases revealed that the monarch has evolved a highly resistant enzyme overall. Nonetheless, we found evidence for relative selectivity of individual cardiac glycosides reaching from 4- to 94-fold differences of inhibition between non-adapted Na⁺/K⁺-ATPase and <i>D. plexippus</i>-Na⁺/K⁺-ATPase. This toxin receptor specificity suggests a mechanism how plants could target herbivores selectively and thus provides a strong basis for pairwise coevolutionary interactions between plants and herbivorous insects.