Positive and Negative Modulation fo Bombyx mori Adenylate Cyclase by 5-Phenyloxazoles: Identification of Octopamine and Tyramine Receptor Agonists

摘要

Nineteen 5-phenyloxoazoles (5POs) were examined for their ability to modulate adenylate cyclase by measuring cAMP produced in head membrane homogeneous of fifth instar larvae of the silkworm Bombyx mori. Among the compounds tested, 5-(4-methoxyphenyl)oxazole (9) and the 2,6-dichlorophenyl congener showed the highest activation of adenylate cyclase; both compounds produced approximately half the level of cAMP produced by the action of octopamine (OCT). The OCT receptor antagonists chloropromazine, mianserin, and metoclopramide attenuated 9-stimulated cAMP production. In contrast, 5-(4-hydroxyphenyl)oxazole (8) and the 4-cyanophenyl congener attenuated both OCT-stimulated and basal cAMP production. The tyramine (TYR) receptor antagonist yohimbine inhibited thenegative effect of 8. These findings indicate that the 5PO class of compounds includes both positive and negative modulators of adenylene cyclase in the heads of B. mori larvae, and that 9 and 8 are OCT and TYR receptor agonist, respectively. These compounds might prove useful for a pharmacological dissection of biogenic amine receptors.