PT - JOURNAL ARTICLE AU - HERBERT SHEPPARD AU - CHARLES R. BURGHARDT TI - The Dopamine-Sensitive Adenylate Cyclase of Rat Caudate Nucleus DP - 1974 Sep 01 TA - Molecular Pharmacology PG - 721--726 VI - 10 IP - 5 4099 - http://molpharm.aspetjournals.org/content/10/5/721.short 4100 - http://molpharm.aspetjournals.org/content/10/5/721.full SO - Mol Pharmacol1974 Sep 01; 10 AB - Various analogues of dopamine were examined for agonist activity with respect to the dopamine-sensitive adenylate cyclase of rat caudate nucleus and the isoproterenol-sensitive enzyme of rat erythrocytes. In both systems decreased activity was associated with 5-methyl, 6-methyl, 2-phenyl, or (R, -)-α-methyl substitution. With the dopamine-sensitive cyclase system N-alkyl, (S, +)-α-methyl, and (R, -)-β-hydroxy substitution resulted in decreased activity, in contrast to results with the isoproterenol-sensitive cyclase. The isomers of the tetrahydroisoquinolines, salsolinol and its N-methylated derivatives, were inactive, lending support to the concept that the nitrogen and catechol moieties were in a trans rather than a gauche conformation. It is suggested that the receptors for the dopamine- and isoproterenol-sensitive adenylate cyclases could have identical primary structures but that they are folded in the membrane in such a way that the binding sites for the active groups of the agonists differ in their relative positions. ACKNOWLEDGMENT The authors wish to acknowledge the assistance of Dr. S. Teitel, Chemical Research Division, in developing the concepts involving stereochemistry.