1-epinephrine, 1-phenylephrine,1-norepinephrine, 1-isoproterenol,cyclic AMP, cyclic GMP,acetylcholine及びcarbacholの各々をマウス腹腔内に投与し,肝5-phosphoribosyl-1-pyrophosphate(PRPP)レベルに及ぼす影響を検討した。catecholaminesのうち,1-epinephrineは肝PRPPを著明に増加した。作用発現までに,5から10分の潜伏期がみとめられた。1-norepinephrine及び1-phenyle phrineは共に有意な上昇作用を示した。1-isoproterenolはPRPPレベルに全く影響を与えなかった。epinephrineの作用は,α-adrenergic blockerであるphenoxybenzamineの前処理により完全に抑制された。dibutyryl cyclic AMPは5-10分間の潜伏時間をおいて,肝PRPP含量を著明に増加させた。dibutyryl cyclic GMPにも肝PRPP含量の増加作用が認められた。この場合には潜伏期は観察されなかった。acetylcholine及びcarbachol投与によっても肝PRPPレベルは増加した。この作用はatropine前処置で阻害されたが,hexamethoniumでは影響されなかった。最後に,ホルモン異常とPRPP及び高尿酸血症との関連性を論じた。

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The mechanisms of the actions of catecholamines on plasma purine catabolites were investigated in rats. The elevations of plasma levels of uric acid and allantoin were caused by two types of mechanisms which included either alpha or beta adrenoceptor-mediated actions. The effect, which was blocked by alpha adrenoceptor antagonist, could be mainly observed in the intraperitoneal treatment with epinephrine, norepinephrine or phenylephrin. e. These catecholamines obviously constricted the blood vessels of portal vein system, resulting in a marked increase of plasma purine catabolites in portal vein blood and a considerable reduction of ATP concentration in intestine and liver. The hepatic extracts prepared from animals administered epinephrine were studied on the amounts of adenine nucleotides, nucleosides and bases therein. The results showed the rapid break-down of hepatic ATP into the end product with a transient accumulation of 5' - AMP. On the other hand, the stimulation of purine catabolism mediated by beta adrenoceptor agonist was closely associated with the reduction of myocardial adenine nucleotides, which has been demonstrated by earlier workers. Isoproterenol caused the reduction of ATP concentration in the myocardium. However, neither compensatory increases of ADP and 5'-AMP nor recognizable amounts of nucleosides and bases were observed. The reduced amounts of myocardial adenine nucleotides by isoproterenol corresponded well to the increased amounts of plasma purine catabolites. Our present studies supported that a rapid breakdown of tissue adenine nucleotides should be more essential action of catecholamine on the increase of plasma purine catabolites, although earlier workers have suggested that catecholamine might induce hyperuricemia by promotion of xanthine oxidase reaction or its renal vasoconstricting action.

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Possible role of catecholamine in a pathogenesis of hyperuricemia was studied in rats and chickens. Although elevation of plasma purine catabolites induced by catecholamine was acute and transient, the action of catecholamine should be taken into consideration for the cause of hyperuricemia. Actually, catecholamine caused prolonged elevation of plasma purine catabolites in rats under severe excretory disturbance by ligating ureters. However, no prolongation of the effect was observed in the animals with lighter degree of excretory disorders. A high correlation between the concentrations of serum uric acid and serum creatinine in hyperuricemic sportsmen has been reported recently. In our experiments in rats, beta adrenoceptor agonists reduced myocardial high-energy phosphate compounds, resulting in highly correlated increases of plasma purine catabolites and plasma creatinine. The rats received stress by fixing showed marked increase of plasma purine catabolites. The increase was inhibited by the pretreatment of sedatives and reserpine, and was partially blocked by adrenoceptor antagonists.These results supported that the increase of plasma purine catabolites might be caused by endogenous catecholamine released by the stress. Successive administrations of catecholamine failed to maintain higher concentration of plasma purine catabolites. However, the effect of beta adrenoceptor agonists on plasma purine catabolites was obviously potentiated by the pretreatment with aminophylline or 11-deoxycorticosterone acetate (DOCA) in rats. Such a potentiation was also observed in chickens, resulting in an abnormally high concentration of plasma uric acid. The chickens received catecholamine together with DOCA under salt-loading showed a remarkable hyperuricemia subjecting to deposition of uric acid in and/or around their organs and tissues. From the results described above, it could be concluded that catecholamine should play a significant role in the induction of hyperuricemia under the specific conditions.

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The analysis of familial ag g r e gation was carried out on the residents in Tooshi island, Mie prefecture, closed community in which outdoor environmental factors are expected to be uniform. The standardized serum uric acid value called “normal quotient” of serum uric acid value were used for the sake of comparative study. This study suggests that gene action may be caused by so called polygene system. In addition to polygenic inheritance, the value of serum uric acid is also influenced by the interaction of genetic and environmental factors. In the parent-chi l d r en analysis, the most consistent relationship was. found in mother and child. There was no significant aggregation of serum uric acid values between spouses, although there was very significant aggregation between siblings. The extent of aggregation of serum uric acid values between siblings was not significantly different from that of mother and child. Consequently, our present study lends further weight to the view that serum uric acid values are influenced mainly by mothers' genetic factors.

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