title: Pharmacological characterisation of the dopamine-sensitive adenylate cyclase in cockroach brain: evidence for a distinct dopamine receptor.
abstract: Dopamine increases cyclic AMP production in crude membrane preparations of cockroach brain with plateaus in cyclic AMP production occurring between 1-10 microM and at 10 mM. Maximal production of cyclic AMP is 2.25 fold greater than that of control values. Octopamine also increases cyclic AMP production with a Ka of 1.4 microM and maximal production 3.5 fold greater than that of control. 5-Hydroxytryptamine does not increase cyclic AMP production. The effects of octopamine and dopamine are fully additive. The vertebrate dopamine agonists ADTN and epinine stimulate the dopamine-sensitive adenylate cyclase (AC) with Ka values of 4.5 and 0.6 microM respectively and with maximal effectiveness 1.7 fold greater than that of control. The selective D2-dopamine agonist LY-171555 stimulates cyclic AMP production to a similar extent with a Ka of 50 microM. Other dopamine agonists (apomorphine, SKF-82526, SKF-38393) have no stimulatory effects. The octopamine-sensitive AC is inhibited by a variety of antagonists known to affect octopamine and dopamine receptors, with the following order of potency: mianserin greater than phentolamine greater than cyproheptadine greater than piflutixol greater than cis-flupentixol greater than SCH-23390 greater than (+)-butaclamol greater than SKF-83566 greater than SCH-23388 greater than sulpiride greater than spiperone greater than haloperidol. The dopamine-sensitive AC is inhibited by the same compounds with the following order of potency: piflutixol greater than cis-flupentixol greater than (+)-butaclamol greater than spiperone greater than or equal to SCH-23390 greater than cyproheptadine greater than SKF-83566 greater than SCH 23388 greater than mianserin greater than phentolamine greater than sulpiride greater than haloperidol. With the exception of mianserin, 3H-piflutixol is displaced from brain membranes by dopamine antagonists with an order of potency similar to that observed for the inhibition of dopamine-sensitive AC. The results indicate that the octopamine- and dopamine-sensitive AC in cockroach brain can be distinguished pharmacologically and the dopamine receptors coupled to AC have pharmacological characteristics distinct from vertebrate D1- and D2-dopamine receptors.
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000201:enzymology*; D003058:Cockroaches; D000242:Cyclic AMP / Q000096:biosynthesis; D004298:Dopamine / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D009655:Octopamine / Q000494:pharmacology; D011954:Receptors, Dopamine / Q000378:metabolism*; D012701:Serotonin / Q000494:pharmacology
chemical_list: D014150:Antipsychotic Agents; D011954:Receptors, Dopamine; D009655:Octopamine; D012701:Serotonin; C028435:2-octopamine; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D004298:Dopamine