Substituent-dependent, positive and negative modulation of Bombyx mori adenylate cyclase by synthetic octopamine/tyramine analogues

Octopamine (OCT)/tyramine (TYR) analogues, mainly including p- and beta -su bstituted phenylethylamines, were prepared as probes for the ligand-binding site(s) of adenylate cyclase-coupled OCT or TYR receptors, and were examin ed for their effects on cAMP production in the head membranes of Bombyx mor i larvae. Small structural changes in OCT and TYR proved to lead to three t ypes of OCT/TYR analogues: (1) compounds that increase the cAMP level by th emselves and also depress OCT-stimulated cAMP production, (2) compounds tha t do not stimulate cAMP production by themselves but inhibit OCT-stimulated cAMP production, and (3) compounds that are not active in either the stimu lation of cAMP production or the inhibition of OCT-stimulated cAMP producti on. Tyramine, which belongs to the second group, also inhibited the basal l evel of cAMP production at high concentrations. The data indicate that two biogenic amine systems that positively and negatively regulate the level of the second messenger cAMP are present in the head part of B. mori larvae. This finding points to the necessity of separately evaluating the positive and negative regulatory effects in order to quantitatively understand the s tructure-activity relationships of OCT receptor ligands, (C) 2001 Wiley-Lis s, Inc.