Characterization of a potent agonist of the insect octopamine-receptor-coupled adenylate cyclase

The imidazoline, 2,3-xylylaminomethyl-2′-imidazoline (XAMI) was evaluated for its effects on octopamine-sensitive adenylate cyclase (OSAC) in crude membrane preparations of neural and non-neural tissues of the American cockroach, Periplaneta americana and ventral-nerve cord homogenates of the tobacco hornworm, Manduca sexta. In the cockroach nerve cord, XAMI was found to be a partial agonist with a V_max 80% of p-octopamine (OA) and a K_a of 30 nM. The affinity is 185 times greater than that of OA. Additivity studies suggest that at maximally stimulating concentrations, XAMI interacts primarily with the OSAC. The antagonist profile for XAMI mimics that of OA with mianserin being the best antagonist, followed by the α-adrenergic antagonist phentolamine. These antagonists were shown to act competitively at the XAMI-binding site. β-adrenergic and dopaminergic antagonists were ineffective. These data indicate that XAMI has the highest reported affinity of any OA-receptor agonist and may be a suitable ligand for studies of the OA receptor.