title: Positive and negative modulation of Bombyx mori adenylate cyclase by 5-phenyloxazoles: identification of octopamine and tyramine receptor agonists.
abstract: Nineteen 5-phenyloxazoles (5POs) were examined for their ability to modulate adenylate cyclase by measuring cAMP produced in head membrane homogenates 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 chlorpromazine, 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 the negative effect of 8. These findings indicate that the 5PO class of compounds includes both positive and negative modulators of adenylate cyclase in the heads of B. mori larvae, and that 9 and 8 are OCT and TYR receptor agonists, respectively. These compounds might prove useful for a pharmacological dissection of biogenic amine receptors.
authors.affiliation: Department of Life Science and Biotechnology, Faculty of Life and Environmental Science, Shimane University, Matsue, Shimane, Japan.
authors.forename: Md Anwar Arfien
authors.initials: MA
authors.lastname: Khan
authors.forename: Toshiya
authors.initials: T
authors.lastname: Nakane
authors.forename: Hiroto
authors.initials: H
authors.lastname: Ohta
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Ozoe
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism*; D018663:Adrenergic Agents / Q000494:pharmacology*; D000818:Animals; D012831:Bombyx / Q000187:drug effects / Q000201:enzymology*; D000242:Cyclic AMP / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D007814:Larva / Q000187:drug effects / Q000201:enzymology; D009655:Octopamine / Q000737:chemistry; D010080:Oxazoles / Q000737:chemistry / Q000494:pharmacology*; D017982:Receptors, Biogenic Amine / Q000819:agonists* / Q000037:antagonists & inhibitors; D014439:Tyramine / Q000737:chemistry
chemical_list: D018663:Adrenergic Agents; D010080:Oxazoles; D017982:Receptors, Biogenic Amine; C027604:norsynephrine receptor; C066175:tyramine receptor; D009655:Octopamine; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D014439:Tyramine