DIHYDROOXADIAZINES - OCTOPAMINERGIC SYSTEM AS A POTENTIAL SITE OF INSECTICIDAL ACTION

Dihydrooxadiazines are structural analogs of octopamine and were compa red with octopamine for their ability to compete with [H-3]dihydroergo cryptine ([H-3]DHE) for binding sites on DHE-sensitive receptors, to s timulate adenylate cyclase activity in nervous system homogenates of P eriplaneta americana L., and to modulate the action of the peptide pro ctolin on the oviducal muscles of Locusta migratoria L. [H-3]DHE bindi ng was inhibited by low concentrations (mu M range) of octopamine, phe ntolamine, N-demethylchlordimeform (DCDM) and several dihydrooxadiazin es. The tested dihydrooxadiazines acted as aminergic agonists in stimu lating cyclic AMP production in cockroach nervous system homogenates a nd did not show additive effects with octopamine, whereas additivity w as observed with 5-hydroxytryptamine. The relative potency of octopami nergic antagonists, including mianserin, cyproheptadine, phentolamine, and gramine, to block octopamine-mediated elevation of cyclic AMP pro duction was similar to the rank-order potency of the same antagonists to inhibit dihydrooxadiazine-mediated elevation of cyclic AMP producti on. Octopamine, 2-(4-bromophenyl)-5,6-dihydro-4H-1,3,4-oxadiazine (4-B r-PDHO), and 8-Br-cyclic AMP caused increased phosphorylation of prote ins that are phosphorylated by exogenously added cyclic AMP-dependent protein kinase. These results indicate that the dihydrooxadiazine-indu ced rise in cyclic AMP levels in homogenates of the cockroach nervous system results directly in activation of an endogenous cyclic AMP-depe ndent protein kinase. 4-Br-PDHO behaved similarly to octopamine in mod ulating the action of proctolin-induced contractions in locust oviduca l muscles. These observations suggest that dihydrooxadiazines act as o ctopamine agonists and have an octopaminergic action in modulating the action of proctolin. Thus, it is proposed that dihydrooxadiazines exe rt at least part of their insecticidal and miticidal actions through i nteraction with the octopaminergic system.