beta-Adrenergic receptor-sensitive adenosine cyclic 3',5'-monophosphate accumulation in homogenates of the rat corpus striatum. A comparison with the dopamine receptor-coupled adenylate cyclase.

The conversion of newly formed [³H]adenosine triphosphate (ATP) to [³H]adenosine cyclic 3′,5′-monophosphate (cAMP) was studied in osmotically shocked, crude synaptosomal fractions of the rat corpus striatum. Of the β-hydroxylated catecholamines tested, the potency of isoproterenol (Ec₅₀ about 0.01 μM) was greater than that of norepinephrine (Ec₅₀ about 1.0 μM). Stereoselectivity was displayed with the (?)isomer of isoproterenol being more potent that its (+)isomer. Of the non-β-hydroxylated catecholamines studied, N-isopropyldopamine demonstrated greater potency than dopamine, whereas apomorphine was inactive. No “additive stimulatory effect” was observed when dopamine was combined with a maximum effective concentration of isoproterenol. The β-adrenergic antagonist propranolol, completely blocked both the dopamine- and norepinephrine-induced increases in cAMP formation. Properties characteristic of a β-type system were, likewise, exhibited by homogenates of both the cerebral cortex and hindbrain. Furthermore, the conversion to [³H]cAMP was increased only slightly (about 16 per cent) by exposure to sodium fluoride, and the stimulatory response to isoproterenol was not altered significantly by high concentrations of ATP but was lost upon sonication of the tissues. In contrast, by assaying adenylate cyclase activity with a high saturating concentration of exogenous [³H]ATP, striatal and cerebral cortical homogenates exhibited responses characteristic of a specific dopamine receptor-coupled adenylate cyclase. Sonication of tissues did not alter the stimulatory effect of dopamine, and sodium fluoride produced about a 2-fold stimulation of the adenylate cyclase activity. Thus, findings in osmotically shocked, crude synaptosomal fractions of the corpus striatum suggest that the paniculate component of adenylate cyclase, which utilizes exogenous ATP as substrate, exhibits properties characteristic of a dopamine receptor-coupled adenylate cyclase. In contrast, the membrane-enclosed, particulate component of adenylate cyclase, which utilizes endogenously synthesized ATP as substrate, conforms to criteria identified with a β-adrenoreceptor-linked adenylate cyclase.