Pharmacological characterization of the locust air sac octopamine receptor

The pharmacology of the locust air sac octopamine receptor was investigated by measuring changes in the concentrations of cyclic 3',5'-adenosine monophosphate (cAMP) after isolated abdominal air sacs were treated with octopamine and related agonists and antagonists. Among the agonists tested only AC-6, clonidine, and compound 1 caused significant increases in cAMP. AC-6 was a full agonist whereas clonidine increased cAMP to 10% that of the octopamine-stimulated level. Compound 1 increased cAMP levers to only 4% of the octopamine-stimulated level. The data from the present study lend weight to the proposal that AC-6's insect toxicity is a result of its activity at the octopamine receptor. All the antagonists tested except yohimbine proved capable of inhibiting octopamine-induced increases in air sac cAMP concentration. The rank order of inhibition efficiency was Mianserin, phentolamine, metoclopromide, and chlorpromazine. This rank order suggested that the air sac receptor is a type 3 receptor, Like the locust neural receptor. However, the high K-i value of metoclopromide for the air sac differed from that for the neural receptor. A novel effect was observed with chlorpromazine, which enhanced octopamine-induced increases in air sac cAMP at low concentrations but had no effect on its own. At higher concentrations chlorpromazine acted as a competitive inhibitor. The sum total of agonist and antagonist effects on the air sac octopamine receptor suggests that it is similar to but not identical to the type 3 neural octopamine receptor described by T. Roeder (Life Sci. 50, 21-28, 1992). (C) 1996 Academic Press