Pharmacological characterisation of the dopamine-sensitive adenylate cyclase in cockroach brain: Evidence for a distinct dopamine receptor

Dopamine increases cyclic AMP production in crude membrane preparations of cockroach brain with plateaus in cyclic AMP production occurring between 1–10 μM 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 μM 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 μM respectively and with maximal effectiveness 1.7 fold greater than that of control. The selective D 2-dopamine agonist LY-171555 stimulates cyclic AMP production to a similar extent with a Ka of 50 μM. 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 > phentolamine > cyproheptadine > piflutixol > cis-flupentixol > SCH-23390 > (+)-butaclamol > SKF-83566 > SCH-23388 > sulpiride > spiperone > haloperidol. The dopamine-sensitive AC is inhibited by the same compounds with the following order of potency: piflutixol > cis-flupentixol > (+)-butaclamol > spiperone ≥ SCH-23390 > cyproheptadine > SKF-83566 > SCH 23388 > mianserin > Phentolamine > sulpiride > 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 D 1- and D 2-dopamine receptors.