Sumio Shima

Effect of adrenergic stimulation on adenylate cyclase activity in rat prostate.

Adrenergic stimulation of the cyclic AMP system of the prostate gland of the rat has been investigated. The observed order of potency for adrenergic agonists in stimulating prostatic adenylate cyclase activity was isoproterenol greater than epinephrine approximately or equal to salbutamol greater than norepinephrine, indicating properties characteristic of beta-2-adrenergic receptor-sensitive adenylate cyclase systems. Dopamine stimulation of the enzyme was exclusively inhibited by a dopamine antagonist, haloperidol, suggesting the presence of dopamine-sensitive receptor in the prostate gland. An initial incubation of the gland with isoproterenol or dopamine resulted in a decrease in maximal enzyme activation by catecholamine, either isoproterenol or dopamine, with no change in hormone affinity. The findings that refractoriness of beta-adrenergic and dopaminergic receptor-adenylate cyclase systems was induced by both receptor-agonists suggest an interaction of an agonist-induced desensitization with another receptor or receptor-enzyme complex in the prostate gland.

Effects of androgen on α- and β-adrenergic receptors in membranes from the rat seminal vesicle

The effects of castration and androgen-replacement on adrenergic receptors in membranes from the rat seminal vesicle were studied. Membranes from seminal vesicles showed saturable and high-affinity binding sites for the beta-adrenergic receptor antagonist, [3H]dihydroalprenolol ([3H]DHA), and the alpha 1-adrenergic receptor antagonist, [3H]prazosin. Castration markedly reduced beta-adrenergic receptors with decreasing the effect of GTP modulating the receptor-ligand affinity, suggesting defects in both the receptor per se and the guanine-nucleotides-regulating mechanism after castration. In contrast, castration increased alpha 1-adrenergic receptors and androgen-replacement reversed this change. The effects of GTP decreasing the alpha 1-receptor binding affinity to the radioligand were observed to a similar extent in the castrated and control membranes. These results demonstrate an inverse regulation by androgen on beta- and alpha 1-adrenergic receptors in membranes of the rat seminal vesicle.

Studies on cyclic nucleotides in the adrenal gland: III. Properties of cyclic AMP- and GMP-dependent protein kinases in the adrenal gland

Abstract Studies have been made on the cyclic nucleotide-binding proteins and cyclic nucleotide-dependent protein kinases in the cortex and the medulla of bovine adrenal glands. The protein kinase from the cortex was more responsive to adenosine 3′,5′-monophosphate (cyclic AMP) than to guanosine 3′,5′-monophosphate (cyclic GMP), with an apparent K m of 0.02 μM for cyclic AMP and of 0.73 μM for cyclic GMP. The enzyme from the medulla, however, was activated to a similar extent by cyclic AMP anp GMP, with an apparent K m of 0.17 μM for cyclic AMP and of 0.18 μM for cyclic GMP. Since the enzyme from the medulla was responsive to cyclic GMP as well as to cyclic AMP, the biological significance of cyclic GMP on the medullary enzyme was discussed. That the activity of cyclic AMP-dependent protein kinases from the cortex is higher than that of the medullary enzyme is due to differences in the cyclic AMP-binding activity of the regulatory proteins associated with the enzyme.

β-adrenergic stimulation of the adenosine 3′,5′- monophosphate system regulated by cholinergc stimuli in the prostate

Abstract Acetylcholine significantly inhibited isoproterenol-stimulated adenosine 3′,5′-monophosphate (cAMP) levels of rat prostatic tissue in a oncentration-dependent fashion. Atrropine but no hexamethonium reversed the inhibitory action of acetylcholine. Tetracaine and verapamil abolished the inhibitory effect of acetylcholine on isoproterenol-stimulated accumulationof cAMP. Exclusion of calcium also eliminated the effect of acetylcholine. Inhibitory regulation of cAMP levels was reproduced by the divalent cation ionophore A23187. These observation suggest that β-adrenergic stimulation of the cAMP system of the prostate is regulated by cholinergic stimulation involving a specific muscarinic receptor with calcium-dependent mechanism sensitive to verapamil or tetracine.

Effects of chronic treatment with adrenocorticotropin on adenylate cyclase activity in the adrenal cortex

The effects of prolonged administration of ACTH in vivo on adenylate cyclase activity in the zona glomerulosa (the capsular fraction) and the zona fasciculata-reticularis (the decapsulated fraction) of rat adrenocortical glands were investigated. Hyperresponsiveness of adenylate cyclase activity to ACTH in vitro was observed for both the capsular and the decapsulated fractions from ACTH-treated rats with a similar magnitude of stimulation by NaF, the guanine nucleotide or forskolin. There were no differences in binding sites for ACTH in membranes between the ACTH- and the saline-treated rats. The augmenting effects of the in vivo ACTH treatment on the enzyme stimulated by ACTH were accompanied by an increased sensitivity to the guanine nucleotide, suggesting that ACTH treatment in vivo was followed by an increased efficacy in coupling of the ACTH receptors to the adenylate cyclase complex associated with the guanine nucleotide regulatory components.

Studies on cyclic nucleotides in the adrenal gland : VI adenyl and guanyl cyclase in the adrenal medulla

Abstract Involvement of the adenyl and guanyl cyclase in the process of catecholamine-release evoked by acetylcholine has been studied in bovine adrenal medulla slices. Stimulation of catecholamine-release by acetylcholine was followed by a late increase in cyclic AMP levels at the time when the secretory stimulation was no longer observed. These results suggest that the delayed activation of the medullary adenyl cyclase is not involved in the secretory process but in the restoration or the synthesis of catecholamine after its release. No changes were demonstrated in cyclic GMP levels during incubation.