A COMPARISON OF THE REGULATORY PROPERTIES OF STRIATAL AND CORTICAL ADENYLATE-CYCLASE

Biochemical properties of adenylate cyclase in striatal and cortical membranes have been analyzed in parallel with their regulation by cholinergic compounds. Striatal adenylate cyclase is more sensitive to forskolin, while the cortical enzyme is more stimulated by GTP. In the presence of GTP, more inhibition by acetylcholine is seen in the cortex than in the striatum. Acetylcholine inhibits striatal adenylate cyclase activity equally in the presence or absence of forskolin but has a diminished ability to inhibit forskolin-stimulated adenylate cyclase in the cortex. The greater sensitivity of cortical muscarinic receptor-coupled adenylate cyclase to EGTA and calcium indicates predominant involvement of the calcium/calmodulin-dependent subtype of the enzyme. The relative effectiveness of antagonists, demonstrating an order of potency of atropine > amitriptyline > pirenzepine > gallamine in reversing the inhibition of adenylate cyclase by acetylcholine for both brain regions, suggests predominantly m4 receptor-mediated responses. These results suggest an m4-type receptor may be coupled to subtypes of adenylate cyclase in the striatum and cortex which differ in their biochemical properties.