Molecular Pharmacology, Vol 13, 512-520, Copyright © 1977 by the American Society for Pharmacology and Experimental Therapeutics

Octopamine-Sensitive Adenylate Cyclase in Cockroach Brain: Effects of Agonists, Antagonists, and Guanylyl Nucleotides

¹ Medical Research Council Neurochemical Pharmacology Unit, Department of Pharmacology, Medical School, University of Cambridge, Cambridge CB2 2QD, England

The pharmacological properties of a cell-free, octopamine-sensitive adenylate cyclase present in homogenates of the brain of the cockroach, Periplaneta americana, have been examined. In accordance with previous reports, octopamine elicited small increases in adenylate cyclase activity in homogenates of both brain and thoracic ganglia. Guanosine 5'-triphosphate, which was routinely included in the assay system, greatly enhanced responses to octopamine, while 5'-guanylylimidodiphosphate greatly increased both basal and octopamine-sensitive adenylate cyclase activities. A variety of phenylethylamines were tested for stimulatory effects upon adenylate cyclase activity in this system: the most potent agonists were found to be octopamine and p-fluorophenylethanolamine. The naturally occurring D(-) isomer of octopamine was over 200 times as potent as the L(+) isomer. A variety of drugs were tested as possible antagonists of the octopamine-sensitive adenylate cyclase; the most potent antagonists were the alpha adrenoceptor antagonist phentolamine and the histamine and 5-hydroxytryptamine antagonist cyproheptadine. A dopamine-sensitive adenylate cyclase was also observed in homogenates of cockroach brain, and was similar to dopamine-sensitive adenylate cyclases in other tissues in its responses to epinine and to the rigid dopamine analogue 2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene, and in the stereoselective blockade of responses to dopamine by the potent neuroleptic agent -flupenthixol. Adenylate cyclase responses to dopamine and octopamine were additive. The structural characteristics necessary for stimulation of octopamine-sensitive adenylate cyclase appear to differ markedly from those required for stimulation of dopamine or beta adrenoceptor-linked adenylate cyclase systems.

Note:
ACKNOWLEDGMENTS The authors are grateful to Dr. L. L. Iversen for helpful criticism of the manuscript, and to Miss Susan Gardiner for expert technical assistance.

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